CA2294300A1 - Urokinase inhibitors - Google Patents

Urokinase inhibitors Download PDF

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Publication number
CA2294300A1
CA2294300A1 CA002294300A CA2294300A CA2294300A1 CA 2294300 A1 CA2294300 A1 CA 2294300A1 CA 002294300 A CA002294300 A CA 002294300A CA 2294300 A CA2294300 A CA 2294300A CA 2294300 A1 CA2294300 A1 CA 2294300A1
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CA
Canada
Prior art keywords
salt
mono
trifluoroacetate
aminoiminomethyl
naphthalenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA002294300A
Other languages
French (fr)
Inventor
Andrew G. Geyer
William J. Mcclellan
Todd W. Rockway
Kent D. Stewart
Moshe Weitzberg
Michael D. Wendt
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Abbott Laboratories
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Individual
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Publication of CA2294300A1 publication Critical patent/CA2294300A1/en
Abandoned legal-status Critical Current

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    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
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    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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    • C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
    • C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
    • C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
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    • C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
    • C07C259/18—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
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    • C07C271/30—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a six-membered aromatic ring being part of a condensed ring system
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    • C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
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    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
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    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/56—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
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    • C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
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    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
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Abstract

Compounds having formula (I) are inhibitors of urokinase and are useful in the treatment of diseases in which urokinase plays a role. Also disclosed are urokinase-inhibiting compositions and a method of inhibiting urokinase in a mammal.

Description

UROKINASE INHIBITORS
Cross Reference to Related Applications S This application is a continuation-in-part of U.S. Application Ser. No.
08/901,040, filed July 25, 1997, pending.
Background of the Invention The present invention provides naphthamidine compounds which inhibit the urokinase t0 enzyme, pharmaceutical compositions containing these compounds and medical methods of treatment using these compounds.
Technical Field Urokinase (urinary-type plasminogen activator or uPA (International Union of 1S Biochemistry classification number: EC3.4.21.31)) is a proteolytic enzyme which is highly specific for a single peptide bond in plasminogen. Plasminogen activation (cleavage of this bond by the urokinase enzyme) results in fonmadon of plasmin, a potent general protease.
Many cell types use urokinase as a key initiator of plasmin-mediated proteolytic degradation or modification of extracellular support structures such as extracellular matrix 20 (ECM) and basement membrane (BM). Cells exist, move and interact with each other in tissues and organs within the physical framework provided by ECM and BM. Movement of cells within ECM or across BM requires local proteolytic degradation or modification of the structures and allows cells to invade adjacent areas previously unavailable prior to the degradation or modification.
25 Cellular invasiveness inflated by urokinase is central to a variety of normal and disease-state physiological processes (Blasi, F., Vassalli, J. D., and Dano, K. J.
Cell Biol. 104:801-804, 1987; Dano, K., Anderson, P. A., Grondahl-Hansen, J., Kristensen, P., Nielsen, L. S., and Skriver, L. Adv. Cancer Res. 44:139-266, 1985; Littlefield, B. A. Ann. N.
Y. Acad. Sci.
622: 167-175, 1991; Saksela, O., Biochim. Biophys. Acta 823: 35-65, 1985;
Testa, J. E. and 30 Quigley, J. P. Cancer Metast. Rev. 9:353-367, 1990). Such processes include, but are not limited to, angiogenesis (neovascularization), bane restructuring, embryo implantation in the uterus, infiltration of immune cells into inflammatory sites, ovulation, spermatogenesis, tissue remodelling during wound repair and organ differentiation, fibrosis, tumor invasion, metastatic SUBSTITUTE SHEET (RULE 26) spread of tumor cells from primary to secondary sites and tissue destruction in arthritis.
Amiloride, for example, a known urokinase inhibitor of only moderate potency, has been reported to inhibit tumor metastasis in vivo (Kellen, J. A., Mirakian, A.
Kolin, A. Anticancer Res. 8:1373-1376, 1988) and angiogenesis/capillary network formation in vitro (Alliegro, M.
C. and Glaser, B. M. J. Cell Biol. I IS[3 Pt 2]: 402a, 1991).
Inhibitors of urokinase, therefore, have mechanism-based anti-angiogenic, anti-arthritic, anti-inflammatory, anti-retinopathic (for angiogenesis-dependent retinopathies), contraceptive and tumoristatic uses.
I~ Summary of the Invention In its principle embodiment, the present invention provides a compound or a pharmaceutically acceptable salt, ester or prodrug thereof, of formula (I) C NH
\ \
'NHZ
A Z-(I), wherein Z is selected from the group consisting of ( 1 ) nitrogen;
(2) methine; and (3) methine substituted with -hfRlR2;
A is selected from the ~~roup consisting of ( 1 ) hydrogen and (2) -LARA>
B is selected from the group consisting of (1) hydrogen and (2j -LBRB and C is selected from the group consisting of (lj hydrogen and (2) -LCRC, with the proviso that at least one of A, B or C is other than hydrogen; and SU8ST1TUTE SHEET (RULE 26) with the proviso that when A is other than hydrogen, at least one of B or C is other than hydrogen, wherein for A, B, and C, Lp, Lg and L~ are independently selected from the group consisting of ( a covalent 1 ) bond, (2) -(CH2)m-(3) -NR1-, (4) -NRZC(X)NR3-, (5) -C(X)-, n (6) -NR2C(X}-, (7) -C(X)NR2-, (8) -CH=CH-, (9) -C=C-, (1()) -O-, ~ ~ ( -S(O)t-, ) ( 12) -C-_-C(CH~)nNR~C(X)-, ( 13) -C(X)NR2(CH2)nC=C-, ( 14) -(CHZ)nNS02-, ( 15) -NR2S02(CH2)nC---C-, 2u ( -C=C(CH2)nNR~SOZNR3-, 16) (17) -NR2SO~NR3(CH2)nC-C-, (18) -S02NR2-, (ly) -NR2S02-, (20) -NR2S02NR3-, 25 (21 -N=N-, ) (22) -C(X)N(OR2)-, (23) -N(ORZ)C(X)-, (24) -HC=CH(CH2)nNR2C(X)-, (25) -(CH2)nNR2C(X)CH=CH-, 3t) (26}-CH=CH{CH2}nNS02-, (27) -NR2S0~(CH2)nCH=CH-, (28) -{CH2)nNR2S02NR3-, (29) -NR2S02NR3(CH2)nCH=CH-, (30) -NR2C(O)O-, SUBSTITUTE SHEET (RULE 26) (31 ) -OC(O)NR2-, (32) -CH=NO-, (33) -ON=CH- and (34} W , wherein W is selected from the group consisting of (a) -O-, (b) -S-, (c} -NRi- and (d) -(CH2)m-, wherein each functional group is depicted with its right-hand end being the end which is attached to the naphthyl or quinolyl ring and its left-hand end being the end which is attached to Rp, Rg or R~;
RA> Rg and R~ are independently selected from the group consisting of ( I ) aryl;
l5 (2) arylalkoxy, wherein the alkylene group is of one to six carbon atoms;
(3) alkyl of one to ten carbon atoms;
(4) alkenyl of two to ten carbon atoms;
{5} alkoxycarbonyl of one to six carbon atoms;
(6) alkynyl of two to ten carbon atoms;
(7) halogen;
(~) -NRIR2>
(9) heterocycle;
( 10) cycloalkenyl of four to twelve carbon atoms;
( I 1 } cycloalkyl of three to twelve carbon atoms:
(12) -NRIC(O)NR2R3; and ( 13) -NR1C(O)Rsp, wherein Rsp is alkyl of one to six carbon atoms;
wherein, at each occurence, R E is selected from the group consisting of (I) hydrogen;
(2) an N-protecting group;
3u (3) alkyl of one to six carbon atoms;
(4) alkenyl of two to six carbon atoms;
(5) alkynyl of two to six carbon atoms:
(f~) aryl;

SUBSTITUTE SHEET (RULE 26) (7) arylalkyl, wherein the alkyiene group is of one to six carbon atoms;
(8) cycloalkyl of three to eight carbon atoms and (9) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms; and wherein, at each occurence, R2 and R3 are independently selected from the group consisting of (1) hydrogen;
(2) alkyl of one to six carbon atoms;
(3) alkenyl of two to six carbon atoms;
(4) alkynyl of two to six carbon atoms;
1t> (5) aryl;
(fi) arylalkyl, wherein the alkylene group is of one to six carbon atoms (7) cycloalkyl of three to eight carbon atoms and (H) c;ycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms; and IS wherein, at each occurence, X is selected from the group consisting of O and (2) S; and wherein, at each occurence, m is one to five, 2U n is zero to four and t is zero to two; and wherein, at each occurence, the alkyl, alkenyl, alkynyl, aryl, heterocycle, cycloalkyl, and cycloalkenyl groups are optionally substituted.
The present invention also relates to a method of inhibiting urokinase in a mammal, 'S particularly humans, by administering a therapeuticaiIy effective amount of a composition comprising a compound of formula (1).
The present invention also relates to pharmaceutical compositions which comprise a therapeutically effective amount of a compound of formula (1j in combination with a pharmaceutically acceptable carrier.
3I) Detailed Description of the Invention As used throughout this specification and the appended claims, the following terms have the meanings specified:

SUBSTITUTE SHEET (RULE 26) The term "alkyl," as used herein, represents a monovalent group derived from a straight or branched chain saturated hydrocarbon by the removal of a single hydrogen atom and is exemplified by methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, neopentyl and the like and may be optionally substituted with one, two, three or four substituents independently a selected from the group consisting of ( 1 ) alkoxy of one to six carbon atoms; (2) alkylsulfinyl of one to six carbon atoms; (3) allcylsulfonyl of one to six carbon atoms; (4) amino; (5) aryl; (6) arylalkoxy, wherein the alkylene group is of one to six carbon atoms; (7) aryloyl; (8) azido; (9) carboxaldehyde; ( 10) cycloalkyl of three to eight carbon atoms; ( I 1 ) halo;
( 12) heterocycle; ( 13) (heterocycle)oxy; ( 14) (heterocycle)oyl; ( 15} hydroxy; ( 16) N-protected amino; ( I7) vitro; ( I 8}
to oxo; ( 19) spiroalkyl of three to eight carbon atoms; (20) thioalkoxy of one to six carbon atoms;
(21 ) -CO?R2; (22) -C(O)NR2R3; (23) -S02R4, wherein R4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (24) -S02NRSR~, wherein R5 and R~, are independently selected from the group consisting of (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl, wherein the alkylene group is of n one to six carbon atoms; (25) -NR7RH, wherein R~ and Rg are independently selected from the group consisting of (a) hydrogen; (b) an N-protecting group; (c) alkyl of one to six carbon atoms; (d) alkenyl of two to six carbon atoms; (e) alkynyl of two to six carbon atoms; (f) aryl;
(g) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (h) cycloalkyl of three to eight carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight ?u carbon atoms, and the alkyIene group is of one to ten carbon atoms, with the proviso that no two groups are bound to the nitrogen atom through a carbonyl group or a sulfonyl group.
The term "alkanoyl," as used herein, represents an alkyl group, as defined herein, attached to the parent molecular group through a carbonyl group, as defined herein, and is exemplified by formyl, acetyl, propionyl, butanoyl and the like.
25 The term "alkenyl," as used herein, represents monovalent straight or branched chain groups containing a carbon-carbon double bond derived from an alkene by the removal of one hydrogen atom and is exemplified by ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl and the like and may be optionally substituted with one, two, three or four substituents independently selected from the group consisting of ( 1 ) alkoxy of one to six carbon 3U atoms; (2) alkylsulfinyl of one to six carbon atoms; (3) alkylsulfonyl of one to six carbon atoms; (4) amino; (5) aryl; (6) arylalkoxy, wherein the alkylene group is of one to six carbon atoms; (7) aryloyl; (8) azido; (9) carboxaldehyde; ( 10) cycloalkyl of three to eight carbon atoms;
( 11 ) halo; ( 12) heterocycle; ( 13) (heterocycle)oxy; ( 14) (heterocycle)oyl; ( I 5) hydroxy; ( I b) N-protected amino; ( 17) vitro; ( 18) oxo; ( 19) spiroalkyl of three to eight carbon atoms; (20) -b-SUBSTITUTE SHEET (RULE 26) thioalkoxy of one to six carbon atoms; (2I ) -C02R2; (22) -C(O)NR2R3; (23) -SOZR4, wherein R4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (24) -SOZNRSRf,, wherein R5 and R6 are independently selected from the group consisting of (a) hydrogen, (b) alkyl, (c) aryl and (d}
arylalkyl, wherein the alkylene group is of one to six carbon atoms; (25) -NR~Rg, wherein R~
and Rg are independently selected from the group consisting of (a) hydrogen;
(b) an N-protecting group; (c) alkyl of one to six carbon atoms; (d) alkenyl of two to six carbon atoms;
(e) alkynyl of two to six carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (h) cycloalkyl of three to eight carbon atoms and (i) cycloalkylalkyl, tU wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms, with the proviso that no two groups are bound to the nitrogen atom through a carbonyl group or a sulfonyl group.
The term "alkoxy," as used herein, represents an alkyl group attached to the parent molecular group through an oxygen atom.
The term "alkoxyalkyl" as used herein, represents an alkyl group to which is attached an alkoxy group.
The term "alkoxycarbonyl," as used herein, represents an ester group; i.e. an alkoxy group, attached to the parent molecular group through a carbonyl group and is exemplified by methoxycarbonyl, ethoxycarbonyl and the like.
The term "alkylene." as used herein, represents a saturated divalent hydrocarbon group derived from a straight or branched chain saturated hydrocarbon by the removal of two hydrogen atoms, and is exemplified by methylene, ethylene, isopropylene and the like.
The term "alkylsulfinyl," as used herein, represents an alkyl group attached to the parent molecular group through an -S(O}- group.
The term "alkylsulfinylalkyl," as used herein, represents an alkyl group, as defined herein, substituted by a sulfinyl group.
The term "alkylsulfonyl," as used herein, represents an alkyl group attached to the parent molecular group through an -S02- group.
The term "alkylsulfonylalkyl," as used herein, represents an alkyl group, as defined 3U herein, substituted by a sulfonyl group.
The term "alkynyl," as used herein, represents monovalent straight or branched chain groups of two to six carbon atoms containing a carbon-carbon triple bond derived from an alkyne by the removal of one hydrogen atom and iS exemplified by ethynyl, I-propynyl, and the like and may be optionally substituted with one, two, three or four substituents SUBSTITUTE SHEET (RULE 26) independently selected from the group consisting of ( 1 ) alkoxy of one to six carbon atoms; (2) alkylsulfinyl of one to six carbon atoms; (3) alkylsulfonyl of one to six carbon atoms; (4) amino; (S) aryl; (6) arylalkoxy, wherein the alkylene group is of one to six carbon atoms; (7) aryloyl; (li) azido; (9) carboxaldehyde; ( I 0) cycloalkyl of three to eight carbon atoms; ( I 1 ) halo;
S ( 12) heterocycle; ( 13} (heterocycle)oxy; ( 14) (heterocycle}oyl; ( 15) hydroxy; ( 16) N-protected amino; ( 17) vitro; ( 18) oxo; ( 19) spiroallcyl of three to eight carbon atoms; (20) thioalkoxy of one to six carbon atoms: (21 ) -C02R2; (22) -C(O)NR2R3; (23) -S02R4, wherein R4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (24) -S02NR5R6, wherein R5 and R6 are independently selected from the group consisting of (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (25) -NR~Rg, wherein R7 and Rg are independently selected from the group consisting of (aj hydrogen; (b) an N-protecting group;
(c) alkyl of one to six carbon atoms; (d) alkenyl of two to six carbon atoms;
(e) alkynyl of two to six carbon atoms; (f) aryl; (g) arylatkyl, wherein the alkylene group is of one to six carbon atoms; (h) cycloalkyl of three to eight carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms, with the proviso that no two groups are bound to the nitrogen atom through a carbonyl group or a sulfonyl group.
The term "amino," as used herein, represents an -Nl-12 group.
2() The term "aminoalkyl," as used herein, represents an alkyl group, as defined herein, substituted by an amino group.
The term "aryl," as used herein, represents a mono- or bicyclic carbocyclic ring system having one or two aromatic rings and is exemplified by phenyl, naphthyl, 1,2-dihydronaphthyl, 1,2,3,4-tetrahydronaphthyl, fluorenyl, indanyl, indenyl and the like and may be optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of ( 1 ) alkanoyl of one to six carbon atoms; (2) alkyl of one to six carbon atoms; (3) alkoxy of one to six carbon atoms; {4j alkoxyalkyl, wherein the alkyl and alkylene goups are independently of one to six carbon atoms; (5) alkylsulfinyl of one to six carbon atoms; (6) alkylsulfinylalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (7) alkylsulfonyl of one to six carbon atoms; (8) alkylsulfonylalkyt, wherein the alkyl and alkylene groups are independently of one to six carbon atoms;
(9) aryl; ( 10) arylalkyI, wherein the alkyl group is of one to six carbon atoms; ( I 1 ) amino; ( 12) aminoalkyl of one to six carbon atoms; ( 13) aryl; ( 14) arylalkyl, wherein the alkylene group is of one to six carbon atoms; ( I S) aryloyl; ( 16) azido; ( 17) azidoalkyl of one to six carbon atoms; ( 18) _g-SUBSTITUTE SHEET (RULE 26) carboxaldehyde; ( 19) (carboxaldehyde)alkyl, wherein the alkylene group is of one to six carbon atoms; (20) cycloalkyl of three to eight carbon atoms; (2 I ) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms and the alkylene group is of one to ten carbon atoms; (22) halo; (23) haloalkyl of one to six carbon atoms; (24) heterocycle;
(25) (heterocycle)oxy; (26) (heterocycle)oyl; (27) hydroxy; (28) hydroxyalkyl of one to six carbon atoms; (29) nitro; (30) nitroalkyl of one to six carbon atoms; (31 ) N-protected amino; (32) N-protected aminoaIkyl, wherein the alkylene group is of one to six carbon atoms; (33) oxo; (34) thioalkoxy of one to six carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (36) -(CH2)qC02R2, wherein q is zero to ~o four; (37) -(CH2)yC(O)NR2R3; (38) -(CH2)qS02R4, wherein R4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (39) -(CHZ)qS02NR5R6, wherein R5 and R~, are independently selected from the group consisting of(a) hydrogen, (b) alkyl, (c) aryl and(d) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (40) -(CH2)qNR7R~, wherein R~ and RR are independently ~5 selected from the group consisting of (a) hydrogen, (b) an N-protecting group, (r) alkyl of one to six carbon atoms, (d) alkenyl of two to six carbon atoms, (e) alkynyl of two to six carbon atoms, (f) aryl, (g) arylalkyl, wherein the alkylene group is of one to six carbon atoms, (h) cycloalkyl of three to eight carbon atoms and (i) cycloaikylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms, with the 2c) proviso that no two groups are bound to the nitrogen atom through a carbonyl group or a sulfonyl group; (41 ) oxo; (42) perfluoroalkyl; (43) perfluoroalkoxy; (44) aryloxy;
(45) cycloalkoxy; (46) cycloalkylalkoxy; and (47) arylalkoxy.
The term "arylalkyl." as used herein, represents an aryl group attached to the parent molecular group through an alkyl group.
25 The term "arylalkoxy," as used herein, represents an arylalkyl group attached to the parent molecular group through an oxygen atom.
The term "aryloxy," as used herein, represents an aryl group which is attached to the parent molecular group through an oxygen atom.
The term "aryloyl," as used herein, represents an aryl group which is attached to the ao parent molecular group through a carbonyl group.
The term "azido," as used herein, represents an -N3 group.
The term "azidoaIkyl," as used herein, represents an alkyl group, as defined herein, substituted by an azido group.
The term "carbonyl," as used herein, represents a C=O group.

SUBSTITUTE SHEET (RULE 26) The term "carboxaldehyde," as used herein, represents a -CHO group.
The term "(carboxaldehydejalkyl," as used herein, represents an alkyl group, as defined herein, substituted by a carboxaldehyde group.
The term "carboxy," as used herein, represents a -C02H group.
s The term "carboxyalkyl," as used herein, represents an alkyl group, as defined herein, substituted by a carboxy group.
The term "cycloalkyl," as used herein represents a monovalent saturated cyclic hydrocarbon group and is exemplified by cyclopropyl, cyclobutyI, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.2. I jheptyl and the like. The cycloalkyl groups of this invention can be Il> optionally substituted with ( 1 ) alkanoyl of one to six carbon atoms; (2) alkyl of one to six carbon atoms; (3) alkoxy of one to six carbon atoms; (4) alkoxyalkyl, wherein the alkyl and alkylene goups are independently of one to six carbon atoms; (5) alkylsulfinyl of one to six carbon atoms; (6) alkyisulfinylalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (7) alkylsulfonyl of one to six carbon atoms; (8) alkylsulfonylalkyl, t5 wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (9) aryl;
( 10) arylalkyl, wherein the alkyl group is of one to six carbon atoms; ( 1 1 j amino; (12) aminoalkyl of one to six carbon atoms; ( 13) aryl; ( 14) arylalkyl, wherein the alkylene group is of one to six carbon atoms; ( 15) aryloyl; ( 16) azido; ( 17) azidoalkyl of one to six carbon atoms;
( 1 R) carboxaldehyde; ( 19) (carboxaldehyde)alkyl, wherein the alkylene group is of one to six 2() carbon atoms; (20) cycloalkyl of three to eight carbon atoms; (21 ) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms and the alkylene group is of one to ten carbon atoms; (22) halo; (23) haloalkyl of one to six carbon atoms: (24) heterocycle;
(2S) (heterocycle)oxy; (2fi) (heterocycle)oyl; (27) hydroxy; (28) hydroxyalkyl of one to six carbon atoms; (29) vitro; (30) nitroa(kyl of one to six carbon atoms; X31 ) N-protected amino; (32) N-25 protected aminoalkyl, wherein the alkylene group is of one to six carbon atoms; (33) oxo; (34) thioalkoxy of one to six carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (36j -(CH2)yC02R2, wherein q is zero to four; (37) -(CH2)qC(O)NR2R3; (38) -(CH2)qS02R4, wherein R4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyi, wherein the alkylene group is of one to six 3o carbon atoms; (39) -(CH2)qS02NR5Rb, wherein R5 and R6 are independently selected from the group consisting of(a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl, wherein the allcylene group is of one to six carbon atoms; (40) -(CHZ)~NR~Rg, wherein R~ and Rg are independently selected from the group consisting of (a) hydrogen, (b) an N-protecting group, (c) alkyl of one to six carbon atoms, (d) alkenyl of two to six carbon atoms, (e) alkynyl of two to six carbon SU9STITUTE SHEET (RULE 26) atoms. (f) aryl, (g) arylalkyl, wherein the alkylene group is of one to six carbon atoms, (h) cycloallcyl of three to eight carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms, with the proviso that no two groups are bound to the nitrogen atom through a carbonyl group or a S sulfonyl group; (41 ) oxo; (42) perfluoroalkyl; (43) perfluoroalkoxy; (44) aryloxy;
(45) cycloaikoxy; (46) cycloalkylalkoxy; and {47) arylalkoxy.
The term "cycloalkenyl," as used herein represents a monovalent cyclic hydrocarbon having at least one carbon-carbon double bond. The cycioalkenyl groups of this invention can be optionally substituted with (I) alkanoyl of one to six carbon atoms; (2) alkyl of one to six icy carbon atoms; (3) alkoxy of one to six carbon atoms; (4) alkoxyaIkyl, wherein the alkyl and alkylene goups are independently of one to six carbon atoms; (5) alkylsulfinyl of one to six carbon atoms; (6) alkylsulfinylaIkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (7) alkylsulfonyl of one to six carbon atoms; (8) alkylsulfonylalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (9) aryl;
l5 ( 10) arylalkyl, wherein the alkyl group is of one to six carbon atoms; ( 11 ) amino; ( 12) aminoalkyl of one to six carbon atoms; ( I3) aryl; ( 14) arylalkyl, wherein the alkylene group is of one to six carbon atoms; ( 15) aryloyl; ( 16) azido; ( 17) azidoalkyl of one to six carbon atoms;
(t!i) carboxaldehyde; (19) (carboxaldehyde)alkyl, wherein the alkylene group is of one to six carbon atoms; (2()) cycloalkyl of three to eight carbon atoms; (21 ) cycloalkylalkyl, wherein the 'o cycloalkyl group is of three to eight carbon atoms and the alkylene group is of one to ten carbon atoms; (22) halo; (23) haloalkyI of one to six carbon atoms; (24) heterocycle;
(25) (heterocycle)oxy; (26) (heterocycle)oyl; (27) hydroxy; (28) hydroxyalkyl of one to six carbon atoms; (29) vitro; (30) nitroalkyl of one to six carbon atoms; (31 ) N-protected amino; (32) N-protected aminoalkyl, wherein the alkylene group is of one to six carbon atoms; (33) oxo; (34) 25 thioalkoxy of one to six carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (3E>) -(CH2)~C02R2, wherein d is zero to four; (37) -(CH2)qC(O)NR2R3; (3IS) -(CH2)yS02R4, wherein R4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (39) -(CH2)~SO2NRSR~,, wherein R5 and R6 are independently selected from the 30 group consisting of(a) hydrogen, (b) alkyl, (c) aryl and(d) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (40) -(CH2)qNR~Rg, wherein R7 and Rg are independently selected from the group consisting of (a) hydrogen, (b) an N-protecting group, (c) alkyl of one to six carbon atoms, {d) alkenyl of two to six carbon atoms, (e) alkynyl of two to six carbon atoms, (f} aryl, (gj arylalkyl, wherein the alkylene group is of one to six carbon atoms, (h) SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTIUS98l15386 cycloalkyl of three to eight carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms, with the proviso that no two groups are bound to the nitrogen atom through a carbonyl group or a sulfonyl group; (41 ) oxo; (42) perftuoroalkyl; (43) perfIuoroalkoxy; (44.) aryloxy;
S (45) cycloalkoxy; (46) cycloalkylalkoxy; and (47) arylalkoxy.
The term "cycloallcoxy," as used herein represents a cycloalkyl group, as defined herein, attached to the parent molecular group through an oxygen atom.
The term "cycloalkylalkoxy," as used herein, represents an alkoxy group, as defined herein, to which is attached a cycloalkyl group.
to The term "cycloalkylalkyl," as used herein, represents a cycloalkyl group, as defined herein, attached to the parent molecular group through an alkyl group.
The term "haloalkyl," as used herein, represents an alkyl group, as defined herein, substituted by one, two, or three halogen atoms and is exemplified by chloromethyl, bromoethyl, trifluoromethyl and the like.
15 The term "halogen," as used herein, represents F, Cl, Br and I.
The term "heterocycle," as used herein, represents a 5-, 6- or 7-membered ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. The 5-membered ring has zero to two double bonds and the 6-and 7-membered rings have zero to three double bonds. The term "heterocycle"
also includes 2U bicyclic, tricyclic and tetracyclic groups in which any of the above heterocyclic rings is fused to one or two rings independently selected from the group consisting of an aryl ring, a cyclohexane ring, a cyclohexene ring, a cyclopentane ring, a cyclopentene ring and another monocyclic heterocyclic ring such as indolyl, quinolyl, isoquinolyl, tetrahydroquinolyi, benzofuryl, benzothienyl and the like. Heterocyc(ics include pyrrolyl, pyrrolinyl, pyrrolidinyl, 2s pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazoiyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, isoindazoyl, triazolyl, 3U tetrazolyl, oxadiazolyl, uricyl, thiadiazolyl, pyrimidyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, dihydroindolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, pyranyl, dihydropyranyl, dithiazolyl, benzofuranyl, benzothienyl and the like.
Heterocyclic groups also include compounds of the formula SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCTlUS98/15386 '~~ F~
~G
~ , wherein F is selected from the group consisting of -CH2-, -CH20- and -O-, and G is selected from the group consisting of -C(O)- and -(C(R')(R"))~ -, wherein R' and R" are independently selected from the group consisting of hydrogen or alkyl of one to four carbon atoms, and v is one to three and includes groups such as 1,3-benzodioxolyi, 1,4-benzodioxanyl and the like. Any of the heterocycle groups mentioned herein may be optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of ( I) alkanoyl of one to six carbon atoms; (2) alkyl of one to six carbon atoms; (3) alkoxy of one to six carbon atoms; (4) alkoxyalkyl, wherein the alkyl and alkylene goups are independently of one to six carbon atoms; (5) alkylsulfinyl of one to six carbon atoms; (6) to alkylsulfinylalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (7) alkylsulfonyl of one to six carbon atoms; (8) alkylsulfonylalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms; (9) aryl; ( 10) aryialkyl, wherein the alkyl group is of one to six carbon atoms; ( 1 1 ) amino; ( 12) aminoalkyl of one to six varbon atoms; (13) aryl; (I4) arylalkyl, wherein the alkylene group is of one to six carbon t 5 atoms; ( I S) aryloyl; ( 16) azido; ( 17) azidoalkyl of one to six carbon atoms; ( 18) carboxaldehyde; ( 19) (carboxaldehyde)alkyl, wherein the alkylene group is of one to six carbon atoms; (20) cycloalkyl of three to eight carbon atoms; (21 ) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms and the alkylene group is of one to ten carbon atoms; (22) halo; (23) haloalkyl of one to six carbon atoms: (24} heterocycle;
(25) 2tt (heterocycle)oxy; (2f~) (heterocycle}oyl; (27) hydroxy; (28) hydroxyalkyl of one to six carbon atoms; (29) vitro; (30) nitroalkyl of one to six carbon atoms; (31) N-protected amino: (32) N-protected aminoalkyl, wherein the alkylene group is of one to six carbon atoms; (33) oxo; (34) thioalkoxy of one to six carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene ~~roups are independently of one to six carbon atoms; (36) -(CH~)~C02R2, wherein d is zero to 25 four; (37) -(CH2)qC(O)NR2R3; (38} -(CHZ)~S02R4, wherein R4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is of one to six carbon atoms;(39) -(CH2)qS02NRSR6, wherein RS and R~, are independently selected from the group consisting of(a) hydrogen, (b) alkyl, (c) aryl and(d) arylalkyl, wherein the alkylene group is of one to six carbon atoms; (40) -(CH2)qNR~Rg, wherein R7 and Rg are independently 3tl selected from the group consisting of (a) hydrogen, (b) an N-protecting group, (c) alkyl of one to six carbon atoms, (d) alkenyl of two to six carbon atoms, (e) alkynyl of two to six carbon SUBSTITUTE SHEET (RULE 26) atoms, (f) aryl, (g) arylalkyl, wherein the alkylene group is of one to six carbon atoms, (h) cycloalkyl of three to eight carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms, with the proviso that no two groups are bound to the nitrogen atom through a carbonyl group or a sulfonyl group; (4I ) oxo; (42) perfluoroalkyl; (43) perfluoroalkoxy; (44) aryloxy;
(45) cycloalkoxy; (46) cycloalkylalkoxy; and (47) arylalkoxy.
The term "(heterocycle)oxy," as used herein, represents a heterocycle group, as defined herein, attached to the parent molecular group through oxygen.
The term "(heterocycle)oyl," as used herein, represents a heterocycle group, as defined herein, attached to the parent molecular group through a carbonyl group.
The term "hydroxy" as used herein, represents an -OH group.
The term "hydroxyalkyl," as used herein, represents an alkyl group, as defined herein, substituted by one to three hydroxy groups, with the proviso that no more than one hydroxy group may be attached to a single carbon atom of the alkyl group and is exemplified by 1 S hydroxymethyl, dihydroxypropyl and the like.
The term "methine" as used herein, represents a =C(H)- group.
The term "N-protected amino," as used herein, refers to an amino group, as defined herein, to which is attached an N-protecting or nitrogen-protecting group, as defined herein.
The term "N-protected aminoalkyl," as used herein, refers to an alkyl group, as defined 2U herein, which is substituted by an N-protecting or nitrogen-protecting group, as defined herein.
The term "nitro," as used herein, represents an -N02 group.
The term "nitroalkyl," as used herein, represents an alkyl group substituted by an -NOZ
group.
The terms "N-protecting group" or "nitrogen protecting group" as used herein, represent 25 those groups intended to protect an amino group against undersirable reactions during synthetic procedures. Commonly used N-protecting groups are disclosed in Greene, "Protective Groups In Organic Synthesis," (John Wiley & Sons, New York ( I9S 1 )), which is incorporated herein by reference. N-protecting groups comprise aryl groups such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, 30 o-nitrophenoxyacetyl, a-chlorobutyryl, benzoyt, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl and chiral auxiliaries such as protected or unprotected D, L or D, L-amino acids such as alanine, leucine, phenylalanine and the like; sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl and the like; carbamate forming groups such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCT/US98/15386 nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-vitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenylyl}-I-methylethoxycarbonyl, a,a-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, alIyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxy carbonyl, fluorenyl-9-methoxycarbonyt, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl and the like; arylalkyl groups such as benzyl, triphenyfmethyl. benzyloxymethyl and the like and silyl groups such as trimethylsilyl and the like. Preferred N-protecting groups are formyl, acetyl, benzoyI, pivaloyl, t-butylacetyl, alanyl, phenylsulfonyl, benzyl, t-butyfoxycarbonyl (Boc) and benzyloxycarbonyl (Cbz).
The term "oxo." as used herein, represents =O.
The term "perfluoroalkyl," as used herein, represents an alkyl group, as defined herein, 5 wherein each hydrogen radical bound to the alkyl group has been replaced by a fluoride radical.
Perfluoroalkyl groups are exemplified by trifluoromethyl, pentafluoroethyl, and the like.
The term "perfluoroalkoxy," as used herein, refers to a perfluoroalkyl group, as defined herein, attached to the parent molecular group through an oxygen atom.
The term "pharmaceutically acceptable salt," as use herein, represents those salts which 2t) are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M Berge, et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, fi6:1-19. The salts can be prepared in situ 25 during the final isolation and purification of the compounds of the invention or separately by reacting the free base group with a suitable organic acid. Representative acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphersulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, 3o heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenyfpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, vaIerate salts and the like.

SUHSTiTUTE SHEET (RUSE 26) Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium and the like, as well as nontoxic ammonium, quaternary ammonium, and amine rations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine and the like.
The term "pharmaceutically acceptable ester," as used herein, represents esters which hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which each alkyl or alkenyI group preferably has not to more than 6 carbon atoms. Examples of particular esters includes formates, acetates, propionates, butyates, acrylates and ethylsuccinates.
The term "pharmaceutically acceptable prodrugs" as used herein, represents those prodrugs of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with with the tissues of humans and lower o animals with undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention.
The term "prodrug," as used herein, represents compounds which are rapidly transformed in vivo to the parent compound of the above formula, for example, by hydrolysis 2o in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, and ludkins, et al.Synthetic Communications, 26(23), 4351-4367 (1996), each of which is incorporated herein by reference.
25 The term "spiroalkyl," as used herein, represents an alkylene diradical, both ends of which are bonded to the same carbon atom of the parent group to form a spirocycliv group.
The term "sulfonyl," as used herein, represents an -SOZ-group.
The term "thioalkoxy," as used herein, represents represents an alkyl group attached to the parent molecular group through a sulfur atom.
30 The term "thioalkoxyalkyl," as used herein, represents an alkyl group substituted by a thioalkoxy group.
Asymmetric or chiral centers may exist in the compounds of the present invention. The present invention contemplates the various stereoisomers and mixtures thereof.
Individual stereoisomers of compounds of the present invention are prepared synthetically from SUBSTITUTE SHEET (RULE 26) commercially available starting materials which contain asymmetric or chiral centers or by preparation of mixtures of enantiomeric compounds followed by resolution well-known to those of ordinary skill in the art. These methods of resolution are exemplified by (1) attachment of a racemic mixture of enantiomers, designated { ~ ), to a chiral auxiliary, separation of the resulting diastereomers by recrystallization or chromatography and liberation of the optically pure product from the auxiliary or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns. Enantiomers are designated herein by the symbols "R" or "S," depending on the configuration of subsitiuents around the chiral carbon atom.
Geometric isomers may also exist in the compounds of the present invention.
The tc~ present invention contemplates the various geometric isomers and mixtures thereof resulting from the arrangement of substituents around a carbon-carbon double bond and designates such isomers as of the Z or E configuration, wherein the term "Z" represents substituents on the same side of the carbon-carbon double bond and the term "E" represents substituents on opposite sides of the carbon-carbon double bond.
IS
Preferred Embodiments Preferred compounds of the present invention have formula (I), wherein A and C are hydrogen and 2U B is -LgRg, wherein -Lg- is -O-, and Rg is alkyl of two to six carbon atoms, and wherein the alkyl group is substituted.
More preferred embodiments of the present invention have formula (I), wherein 25 A is -LARp and B and C are hydrogen, wherein -LA- is selected from the group consisting of ( 1 ) a covalent bond, (2) -{CH2)m-, 30 (3) -NR2C(X)-, (4) -C(X)NR2-, (5) -NR2C(X)NR3-, {6) -C=C-, (7) -CH=CH-, _17_ SUBSTITUTE SHEET (RULE 26) (8) -C(X)NR2(CH2)nC=C_ (9) -C(X)-, ( 10) _O_, ( 11 ) -OC(O)NR~- and ( 12) W ; and wherein Rp is selected from the group consisting of ( 1 ) amino;
(2) aryl;
is (3) alkyl of one to ten carbon atoms;
(4} arylalkyl, wherein the alkylene group is of one to ten carbon atoms;
(5) cycloalkyl of three to eight carbon atoms;
(6) arylalkoxy, wherein the alkylene group is of one to ten carbon atoms and (7) heterocycle, wherein the heterocycle is selected from the group consisting of ( 1 ) furanyl, (2) thienyl and (3) imidazolyl; and wherein, at each occurence, R2 is selected from the group consisting of ( 1 ) hydrogen and (2) alkyl of one to six carbon atoms; and wherein, at each occurence, m ~s two, n ~s one, R ~ and R3 are hydrogen, W and X are O, aryl is phenyl, the alkyl group and the aryl group are optionally substituted and the alkenyl group is substituted.
Srill more preferred compounds of the present invention have formula (I), wherein A and B are hydrogen;

SUBSTITUTE SHEET (RULE 2S) C is -LCR~;
-L~- is selected from the group consisting of ( 1 ) a covalent bond, (2) -OC(O)NR2-, (3) -S02NR2-, (4) -C(X)NR2-, {5) -NRI- and to (6) -O-;
R~ is selected from the group consisting of ( 1 ) alkyl of one to six carbon atoms;
(2) aryl:
I5 (3) arylalkyl, wherein the alkylene group is of one to six carbon atoms and (4) hererocycle, wherein the heterocycle is selected from the group consisting of ( 1 ) furanyl;
(2) pyrimidinyl; and I w Fv G
(3) ~ ~ , wherein F is -O-, G is -(C(R')(R"))~-, R' and R" are hydrogen and v is 20 one;
X is O; and wherein, at each occurence, R I and R2 are H, aryl is phenyl and ''S the alkyl is optionally substituted.
Still more preferred compounds of the present invention have formula (I) wherein A is -LpRp, B is -LgRg, C is hydrogen, 30 -Lp- and -Lg- are -O-, and Rp and Rg are alkyl of one to six carbon atoms.
Still more preferred compounds of the present invention have formula (I) wherein SUBSTITUTE SHEET (RULE 26) A is -LpRp, B is -LgRg, C is -L~R~, -Lp-, -Lg-, and -L~- are -O- and Rp, Rg, and R~ are alkyl of one to six carbon atoms.
Still more preferred compounds of the present invention have formula (I) wherein A is hydrogen;
B is -LgRg;
C is -L~RC;
lU -Lg- is -O-;
-LC- is selected from the group consisting of ( 1 ) a covalent bond, (2) -O-, (3) -CH=CH-, t5 (4) -NRt- and (S) -NR2C(O)O-;
Rg is selected from the group consisting of ( 1 ) alkyl and (2) arylalkyl, wherein the alkylene group is of one to six carbon atoms;
2t) R~ is selected from the group consisting of ( 1 ) alkyl of one to six carbon atoms;
(2) alkenyl of one to six carbon atoms;
(3) halogen;
(4) aryl and 25 (5) heterocycle, wherein the heterocycle is selected from the group consisting of (I) benzofuranyl;
(2) tetrahydrofuranyl;
(3) pyrimidinyl;
3t) (4) pyrazolyl;
(5) furanyl;
(6) pyrimidinyl;
(7) thiazolyl and SUBSTITUTE SHEET (RULE 26) F~
G
(8) ~ ~ , wherein F is -O-. G is -(C(R')(R"))v -, R' and R" are hydrogen and v is one; and wherein, at each occurence, aryl is phenyl and alkyl, aryl and heterocycle are optionally substituted.
Preferred compounds falling within the scope of formula (I) include:
7, 8-dimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
6, 7, 8-trimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt ;
fi, 7-dimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt ;
tU 2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy)acetamide mono(trifluoroacetate) salt;
7-benzyloxy-X-iodo-2-naphthalenecarboximidarnide mono(trifluoroacetate) salt;
methyl [(7-aminoiminomethyl-2-methoxy-I-naphthalenyl)oxyJacetate mono{trifluoroacetate) salt;
2-[(7-aminoiminomethyl-2-methoxy-I-naphthalenyl)oxyJ-yl-acetic acid mono(trifluoroacetate) 1 S salt;
N-[4-(aminomethyl)phenylJ-h-aminoiminomethyl-2-naphthalenecarboxamide bis(trifluoroacetate) salt;
N-[4-(amino)phenyl]-fi-aminoiminomethyl-2-naphthalenecarboxamide bis(trifluoroacetate) salt;
I-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-hydroxypropane 2cl mono(trifluoroacetatej salt;
phenylmethyl [7-{aminoiminomethyl)-1-naphthalenyl)carbamate mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl)acetamide mono(trifluoroacetate) salt;
methyl [7-(aminoiminomethyl)-1-naphthalenyl)carbamate mono(trifluoroacetatej salt;
methyl 3-[[7-(aminoiminomethyl)-1-naphthalenyl]amino-3-oxopropanoate 25 mono(trifluoroacetate) salt;
N-[7-(aminoiminomethylj-1-naphthalenyi]-2-(phenylmethoxyjacetamide mono(trifluoroacetate) Salt;
N-[7-(aminoiminomethyl )- I -naphthalenyl J-1,3-benzodioxole-5-carboxamide mono(trifluoroacetate) salt;
3U N-[7-(aminoiminomethyl)-1-naphthalenyl]benzenemethanesulfonamide mono(trifluoroacetate) salt;

SUBSTITUTE SHEET (RULE 26) 1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-brornopropane mono{hydrochloride) salt;
3-[(7-aminoiminomethyl-2-methoxy-I-naphthalenyl)oxy]propene mono(trifluoroacetate) salt;
1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-phenylpropane mono(hydrochloride) salt:
1-( (7-aminoiminomethyl-2-methoxy-1-naphthalenyl foxy]-3-[ I -(3,4-dimethoxy)phenyl]-propane mono(hydrochloride) salt;
7-methoxy-8-{2-furanyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
methyl f~-(aminoiminomethyl)-4-[(methoxycarbonyl)anuno]-2-naphthalenecarboxylate IU mono(trifluoroacetate) salt;
(E)-(7-methoxy-8-[2-(Phenyl)ethenyl])-2-naphthaleneimidamide mono{trifluoroacetate) salt 6-(4-phenylbutynyl)-2-naphthalenecarboximidarnide mono(trifluoroacetate) salt;
7-(2-hydroxyethoxy)-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-(2-hydroxyethoxy)-2-naphthalenecarboximidanude mono(trifluoroacetate) salt;
fi-(4-methyl-1-pentynyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
f~-(5-phenylpentynyl)-2-naphthalenecarboximidamide mono(trifluoroacetate>
salt;
6-(3-phenyl-I-propynyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
fi-(phenylethynyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
3-amino-N-[3-[6-(aminoiminomethyl)-2-naphthalenyl J-2-propynyl]benzamide 20 mono{trifluoroacetate) salt;
4-amino-N-(3-(6-aminoiminomethyl-2-naphthalenyl)-2-propynyl]benzamide mono(trifluoroacetate) salt;
(S)-2-amino-N-[ 1-[(6-aminoiminomethyl-2-naphthalenyl)carbonyl]cyclohexyl]propionamide bis(trifluoroacetate) salt:
~5 fi-methoxy-K-benzyloxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt:
2-[(7-aminoiminomethyl-3-methoxy-I-naphthalenyl)oxyJacetamide mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-phenylurea mono(trifluoroacetate) salt;
(E)-6-[2-(phenyl)ethenyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
6-[2-(phenyl)ethyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
3U 7-propoxy-!~-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
( ~ )- 6-(3-phenyloxiranyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
(E)-6-[2-(2-thienyl)ethenyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
6-(3-oxobutyl)-2-naphthalenecarboximidamide mono{trifluoroacetate) salt;
6-(3-methoxyphenyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;

SUisSTITUTE SHEET (RULE 26) N-[3-(methyl)phenyl]-6-aminoiminomethyl-2-naphthalenecarboxamide mono(trifluoroacetate) salt;
6-(2-formylphenoxy)-2-naphthalenecarboximidamide mono(trifluoroacetatej salt;
6-(2-formylphenyl)-2-naphthalenecarboximidamide mono{trifluoroacetate) salt;
6-[2-(hydroxymethyl)phenyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
6-(3-oxo-1-butenyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-K-(1H-pyrazol-4-yl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
N-phenyl-6-aminoiminomethyl-2-naphthalenecarboxamide mono(methanesulfonate) salt;
lOf 4-[{6-aminoiminomethyl-2-naphthalenyl)oxy]-N-methylbenzeneacetamide mono(trifluoroacetate) salt;
6-[2-(methylthio)phenyl]-2-naphthalenecarboximidamide mono(methanesulfonate) salt;
fi-[2-(2-thiomethoxoxyethyl)phenyl]naphthalene-2-carboximidamide mono{methanesulfonate) salt;
t5 7-methoxy-?i-(3-furanyl)-2-naphthalenecarboximidamide mono(methanesulfonate} salt;
7-rnethoxy-H-(2-benzofuranyl)naphthalene-2-carboximidamide mono(methanesulfonate) salt;
(E)-H-[2-( 1,3-benzodioxol-5-yl)ethenyl ]-2-naphthalenecarboximidamide mono(methanesulfonate) salt;
( ~ )-7-methoxy-H-(tetrahydro-3-furanyl)-2-naphthalenecarboximidamide 2O mono(methanesulfonate) salt;
f~-[[4-(2-aminoethyl)phenyl]ethynyl]-2-naphthalenecarboximidamide mono(trifluoroacetate}
salt;
7-methoxy-R-[2-pyrimidinyl(oxy)]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-~-[2-thiazoyl(oxy))naphthalene-2-carboximidamide mono(trifluoroacetate) salt;
S 7-methoxy-H-(4-nitrophenoxy)-2-naphthalenecarboximidamide mono(trifluoroac;etate) salt;
7-methoxy-li-pentafluorophenoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-X-[N-2-pyrimidinyl(amino)j-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-benzylurea mono(trifluoroacetate) salt;
3c~ N-(6-aminoiminomethyl-2-naphthalenyl)-N'-methylurea mono(trifluoroacetate) salt;
N-(b-aminoiminomethyl-2-naphthalenyl)-N'-isopropylurea mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-phenyl-N'-methylurea mono(trifluoroacetate) salt;
fi-aminonaphthalene-2-carboximidamide mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-cyclohexylurea mono(trifluoroacetate}
salt;

SUBSTITUTE SHEET (RULE 26) N-(6-aminoiminomethyl-2-naphthalenyl)-N'-benzyloxyurea mono(trifluoroacetate) salt;
l,l-dimethylethyl [4-[[(6-cyano-2-naphthalenyl)amino]carbonyl]phenyl]carbamate mono(trifluoroacetate) salt N-[6-(aminoiminomethyl)-2-naphthalenyl]-4-(aminomethyl)benzamide mono(trifluoroacetatej salt;
ethyl (6-(aminoiminomethyl)-2-naphthalenyl]carbamate mono{trifluoroacetate) salt;
l,l-dimethylethyl [4-[[[fi-aminoiminomethyl)- 2-naphthalenyl)amino]carbonyl]amino]phenyl]
carbamate mono(trifluoroacetate) salt;
(E)-6-[2-(phenylthio)ethenyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
lip (E)-6-[2-(2-furanyl)ethenyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
(E)-6-[2-(1H-imidazol-1-yl)ethenyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
(E)-4-[2-(6-aminoiminomethyl-2-naphthalenyl)ethenyl]benzenesulfonamide mono(trifluoroacetate) salt;
(E)-4-[2-(6-aminoiminomethyl-2-naphthalenyl)ethenyl]benzoic acid mono(trifluoroacetate) salt;
os 4-[7-(aminoiminomethyl)-2-methoxy-I-naphthalenyt]dihydro-2(3H)-furanone rnono(trifluoroacetate) salt;
7-methoxy-k-(1-acetyl-1H-pyrazolyl)-2-naphthalenecarboximidamide mono{trifluoroacetate) salt;
7-methoxy-8-( 1-(methylsulfonyl)-1H-4-pyrazolyl]-2-naphthalenecarboximidamide 20 mono(trifluoroacetate) salt;
(E)-4-[2-(6-aminoininomethyl-2-naphthalenyl)ethenyl]benzamide mono(trifluoroacetate) salt;
6-[2-(4-aminophenyl)ethoxy]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
methyl [3-methoxy-6-(aminoiminomethyl)-4-naphthalenyl]carbamate mono(trifluoroacetate) salt;
25 7-methoxy-8-[2-pyrimidinyl(amino)]-2-naphthalenecarboximidamide bis(trifluoroacetate) salt;
fhthalenecarboxamide, mono(trifluoroacetate) salt;
fi-(4-aminophenyl)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
methyl 2-[4-[[[6-(aminoiminomethyl)-2-naphthalenyl]carbonyl]amino]-phenoxy]acetate,mono(trifluoroacetate) salt;
3c) {E)-6-[2-[(3-hydroxymethyl)phenyl]ethenyl)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
6-(2-phenyl-1-cyclopropyl)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
(E)-6-[2-[4-(aminomethyl)phenyl]ethenyl]-?-naphthalenecarboximidamide, bis(trifluoroacetate) salt;

SUBSTITUTE SHEET (RULE 26) (E)-6-[2-[4-( I ,2-dihdyroxyethyl)phenyl]ethenyl]-2-naphthalenecarboximidamide, rnono(trifluoroacetate) salt;
(E)-6-[2-[4-( 1 R-amino-2-hydroxyethyl}phenyl)ethenylJ-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
7-methoxy-8-(2-pyrimidinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
(E)-6-[2-[[4-(dimethylamino)methyl]phenyl]ethenyl]-2-naphthalenecarboximidamide, bis(tllfluoroacetate) salt;
(E)-6-[2-[4-(hydroxymethyl}phenyl]ethenyl]-2-naphthalenecarboximidamide.
mono(trifluoroacetate) salt;
lU 4-[[6-(aminoiminomethyl)-2-naphthalenyl]ethynyl]-L-phenylalanine, mono(trifluoroacetate) salt;
6-(3-formylphenyi)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
(E)-fi-[2-( 1,2,3,4-tetrahydro-fi-isoquinolinyl)ethenylj-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
n (E)- fi-[2-[3-(2-hydroxyethyl)phenyl]ethenyl]-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(2,3-dihydro-1 H-inden-S-yl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
f-[(4-aminophenyl)ethynyl]-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
2U I,1-dimethylethyl [2-[3-[[6-(aminoiminomethyl)-2-naphathalenyl)ethynyl]-6-methoxyphenyl)ethyl]carbamate, mono(trifluoroacetate) salt;
I,1-dimethylethyl [[4-[[6-(aminoiminomethyl)-2-naphathalenyl]ethynylJ-phenyl Jmethyl]carbamate, mono(trifluoroacetate) salt;
f~-[[4-(aminomethyl)phenylJethynyl]-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
'_, ~-[[3-(2-aminoethyl)-4-methoxyphenylJethynyl)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
fi-[[4-(hydroxymethyl)phenyl]ethynyl]-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt:
6-[( I ,2,3,4-tetrahydro-6-isoquinolinyl)ethynyl j-2-naphthalenecarboximidamide, 3o bis(trifluoroacetate) salt;
f~-(aminoiminomethyi)-N-(4-methylphenyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
I,l-dimethylethyl [[4-[[[fi-(aminoiminomethyl)-2-naphathalenyl]aminoJ-carbonyl)phenylJmethylJcarbarnate, mono(trifluoroacetate) salt;

SUBSTITUTE SHEET (RULE 26) N-[6-(aminoiminomethyl)-2-naphthalenyl)benzamide, mono(trifluoroacetate) salt;
1,1-dimethylethyl [[4-[[[6-(aminoiminomethyl)-2-naphathalenyl]amino]carbonyl]-cyclohexyll]methyl]carbamate, mono(trifluoroacetate) salt;
N-(6-(aminoiminomethyl)-2-naphthalenyl]-N'-(4-aminophenyl)urea, bis(trifluoroacetate) salt;
N-[6-(aminoiminomethyl)-2-naphthalenyl]-4-4-(aminomethyl)cyclohexanecarboxamide, bis(trifluoroacetate) salt;
N-[6-(aminoiminomethyl)-2-naphthalenyl]-N'-[(4-aminomethyl)phenyl] urea, bis(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(4-ethylphenyl)-2-naphthalenecarboxamide, acetate salt;
tU C~-(aminoiminomethyl)-N-(2-naphthalenyl)-2-naphthalenecarboxanude, mono(tlifluoroacetate) salt;
6-(5-phenyl-2-oxazolyl)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
6-(5-phenyl-2-thiazoIyl)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
E~-(aminoiminomethyl)-N-( 1,2,3,4-tetrahydro-f~-quinolinyl)-2-naphthalenecarboxamide, t 5 bis(trifluoroacetate) salt;
6-[amino(hydroxyimino)methyl]-N-phenyl-2-naphthalenecarboxamide;
6-[4-[(hydroxymethyl)phenyl]methoxy]-2-naphthalenecarboximidamide, methanesulfonate salt;
6-(2-pyridinylethynyl)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
N-[4-(aminocarbonyl)phenyl)-6-(aminoiminomethyl)-2-naphthalenecarboxamide, 20 mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(2-thiazolyl)-2-naphthalenecarboxamide, monohydrochloride 6-(aminoiminomethyl)-N-(6-methoxy-3-pyridinyl)-2-naphthalenecarboxamide, monohydrochloride fi-(aminoiminomethyl)-N-( 1,3-benzodioxol-5-yl)-2-naphthalenecarboxamide, 2> mono(trifluoroacetate) salt;
f~-(aminoiminomethyl)-N-( 1,2,3,4-tetrahydro-2,4-dioxo5-pyrimidinyl)-2-naphthalenecarboxamide, monohydrochloride 6-(aminoiminomethyl)-N-(3,5-difluorophenyl}-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
30 E~-(aminoiminomethyl)-N-(1H-pyrazol-3-yl}-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
fi-(aminoiminomethyl)-N-(5-methyl-3-isoxazolyll)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
f~-(aminoiminomethyl)-N-(pyrazinyl)-2-naphthalenecarboxamide, mono(trifluoroacetate} salt;

SUBSTITUTE SHEET (RULE 26) f~-(aminoiminomethyl)-N-(6-methyl-2-pyridinyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(3,4,5-trimethoxyphenyl)-2-naphthalenecarboxamide, monohydrochloride 6-(aminoiminomethyl)-N-(3-methyl-2-pyridinyI)-2-naphthalenecarboxamide, bis(trifluoroacetate) salt;
fi-(aminoiminomethyl}-N-(5-bromo-2-thiazolyll)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(5-methyl-2-pyridinyl)-2-naphthalenecarboxamide, tU mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(4-methyl-2-thiazolyl)-2-naphthafenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(6-quinolinyl)-2-naphthalenecarboxamide, bis(trifluoroacetate) salt;
15 6-(aminoiminomethyl)-N-( 1 f-1-indazol-6-yl)-2-naphthalenecarboxamide, bis(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-( I H-indazol-5-yl)-2-naphthalenecarboxamide, bis(trifluoroacetatej salt;
f~-(aminoiminomethyl)-N-( 1 H-indol-5-yl)-2-naphthalenecarboxamide, 2U mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(5-pyrimidinyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
E~-(aminoiminomethyl)-N-(3-pyridazinyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt:
25 fi-(aminoiminomethyl)-N-(5-bromo-2-pyridinylj-2-naphthalenecarboxamide, mono(trifluoroacetate) salt:
f~-(aminoiminomethyl)-N-[ 3-( 1-methylethoxy)phenyl ]-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-( 1 H-imidazolyl)-2-naphthalenecarboxamide, 3o bis(trifluoroacetate) salt;
6-[2-[4-(hydroxymethyl)phenylJ-1-cyclopropyl]-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
N-(ethoxycarbonyl)-6-(2-phenyl- I -cyclopropyl)-2-naphthalenecarboximidamide 6-(aminoiminomethyl)-N-(2-methyl-6-quinolinyl)-2-naphthalenecarboxamide, SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCT/US98l15386 bis(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(3-propoxyphenyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-[3-( 1-ethylpropoxy jphenyl]-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-[3-(cyclopentyloxy)phenyl]-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-(3-phenoxyphenyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
l 6-(aminoiminomethyl)-N-[3-(phenylmethoxy)phenyl]-2-naphthalenecarboxamide, mono(trifluoroacetatej salt;
6-(aminoiminomethyl)-N-(3-ethoxyphenyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
f~-(aminoiminomethyl)-N-(4-nitrophenyl)-2-naphthalenecarboxamide, I5 rnono(trifluoroacetate) salt;
fi-(aminoiminomethyl)-N-[3-(cyclobutylmethoxy)phenyl]-2-naphthalenecarboxamide,mono(trifluoroacetate) salt;
6-[amino(ethoxycarbonyl)iminoJ-N-[3-( I-methylethoxy)phenyl]-2-naphthalenecarboxamide;
6-(aminoiminomethyl)-4-[5-(ethylsulfonylj-3-furanyl]-N-phenyl-2-naphthaienecarboxamide, 20 monohydrochloride;
methyl [7-(aminoiminomethyl)-2-methoxy-1-naphthalenyl)carbamate, mono(trifluoroacetate) salt;
7-methoxy-8-(2-pyrimidinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
7-methoxy-8-[(phenylmethyl)amino]-2-naphthalenecarboximidamide, 25 mono(trifluoroacetate) salt;
7-methaxy-8-(phenylamino)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
7-methoxy-H-[(4-methoxyphenyl)aminoJ-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
(E)-3-[7-(aminoiminomethyl)-2-methoxy-1-naphthalenyl)-2-propenamide, 30 mono(trifluoroacetate) salt;
7-methoxy-8-(3-oxo- I -cyclopenten- I -yl)-2-naphthalenecarboxi midamide, mono(trifluoroacetate) salt;
methyl 4-[[[7-(aminoiminomethyl)-1-(2-pyrimidinylamino)-2-naphthalenyl]oxy]methylJbenzoate, mono(trifluoroacetate) salt;

SUBSTITUTE SHEET (RULE 26) 4-[[[7-(aminoiminomethyl)-1-(2-pyrimidinylamino)-2-naphthalenyl ]oxy]methyl]
benzoic acid, mono(trifluoroacetate) salt;
7-methoxy-8-(pyrazinyloxy)-2-naphthalenecarboximidamide, dimethanesulfonate salt;
7-methoxy-8-(phenylthio)-2-naphthalenecarboximidamide, methanesulfonate;
7-methoxy-8-(pyrazinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
methyl 5-[7-[(aminoiminomethyl)-2-naphthalenyl]oxy]pentanoate, mono(trifluoroacetate) salt;
5-[[6-(aminoiminomethyl)-2-naphthalenyl]oxy]pentanoic acid, mono(trifluoroacetate) salt;
methyl 4-[[[7-amino(hydroxyimino)methyl]-2-naphthalenyl]oxy]methyl]benzoate;
methyl 2-[[6-(aminoiminomethyl)-2-naphthaIenyl]oxy]acetate, mono(trifluoroacetate) salt;
1U 7-[2-(4-morpholinyl)ethoxy]-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
2-[[6-(aminoiminomethyl)-2-naphthalenyl]oxy]acetic acid, mono(trifluoroacetate) salt;
methyl 4-[fi-(aminoiminomethyl)-2-naphthalenyl]oxy]methyl]benzoate, mono(trifluoroacetate) salt;
methyl [7-(aminoiminomethyl}-1-naphthalenyl]methylcarbamate, mono(trifluoroacetate) salt;
n propyl [7-(aminoirninomethyl)-1-naphthalenyl]carbamate, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl}-1-naphthalenyl]-N'-methylurea, mono(trifluoroacetate) salt;
ethyl [7-(aminoiminomethyl)-1-naphthalenyl)carbamate, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl)propanamide, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl)-2-methoxyacetamide, mono(trifluoroacetate) salt;
2u N-[7-(aminoiminomethyl)-1-naphthalenyl]urea, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl]-2-hydroxyacetamide, mono(trifluoroacetate) salt;
H-(2-pyrimidinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
H-amino-2-naphthalenecarboximidanude, bis(trifluoroacetate) salt;
)i-(2-pyridinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
?5 N-hydroxy-H-(2-pyrimidinylamino)- 2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
fi-(aminoiminomethyl)-4-(3-furanyl )-N-[4-(trifluoromethyl)phenyl]-2-naphthalenecarboxamide.
mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-4-(3-furanyl)-N-(4-pyridinyl)-2-naphthalenecarboxamide, 3U dihydrochloride;
f~-(aminoiminomethyl)-4-(3-furanyl)-N-( 1 H-pyrazol-3-yl)-2-naphthalenecarboxamide, dihydrochloride;
6-(aminoiminomethyl)-4-(3-furanyl)-N-(3-pyridinyl)-2-naphthalenecarboxamide, dihydrochloride;

SUBSTITUTE SHEET (RULE 26) WO_, 99/0509( _ PCTIUS98/15386, methyl (7-(aminoiminomethyl)-3-[[[4-(aminomethyl)phenyl]amino]carbonyl]-1-naphathalenyl]carbamate, bis(trifluoroacetate) salt;
6-(aminoiminomethyl)-4-(3-furanyl)-N-(2-pyridinyl)-?-naphthalenecarboxamide, dihydrochloride;
fi-(aminoiminomethyl)-4-(3-furanyl)-N-phenyl-2-naphthalenecarboxamide, monohydrochloride 6-(aminoiminomethyl)-4-[ t -(methylsulfonyl)-1 H-pyrazol-4-yl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
h-(aminoiminomethyl)-4-[5-(methylthio)-3-furanyl)]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
U) 6-(aminoiminomethyl)-N-[4-(aminomethyl)phenyl]-4-(2-pyrimidinylamino)-2-naphthalenecarboxamide, tris(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-phenyl-4-(2-pyrimidinylarnino)-2naphthalenecarboxamide, mono(trifluoroacetatej salt;
N-[(4-(aminomethyl)phenyl]-6-[amino(hydroxyimino jmethyl]-4-(2-pyrimidinylamino)-2-t S naphthalenecarboxamide, bis(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-[4-(hydroxymethyl)phenyl]-4-(2-pynmidinylaminoj-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
methyl [3-[[[4-(aminomethyl)phenyl]amino]carbonyl]-7-[4-amino(hydroxyiminojmethyl]-I-naphthalenyl]carbamate, bis(trifluoroacetate) salt;
2(> fi-(aminoiminomethyl)-N-phenyl-4-(tetrahydro-3-furanyl)-2-naphthalenecarboxamide,monohydrochloride;
f~-[amino(,hydroxyimino)methyl]-N-phenyl-4-(2-pyrimidinylamino)-2-naphthalenecarboxamide 6-{aminoiminomethyl)-4-[5-(ethylthio)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide,monohydrochloride;
25 fi-(aminoiminomethyl)-4-[5-(propylthio)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide,monohydrochloride;
fi-(aminoiminomethyl)-N-phenyl-4-(2-pyrrolidinyl )-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-4-[5-(propyisulfonyl)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, act monohydrochloride;
6-(aminoiminomethyI)-4-[5-[methylthio)methyl]-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
fi-(aminoiminomethyl)-4-[5-(methoxymethyl)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCT/US98115386 6-(aminoiminomethyl)-4-[5-(methylsulfonyl)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, mono(trifluoroacetate) salt; and 6-(aminoiminomethyl}-4-[5-(ethythio)tetrahydro-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride.
Determination of Urokina a inhibition The efficacy of the compounds of this invention as urokinase inhibitors was determined by measuring the inhibition of the urokinase enzyme Abbokinase (Abbott Laboratories, Abbott Park, IL) on substrate S-2444, of formula pyroGlu-Arg-pNA-HCl (DiaPharma Group, Inc.
1o Distributor of Chromogenix) at 200 ~M.
The assay was performed in a 96 well polystyrene, flat bottom plate in a 50 mM
Tris/0.15 M NaCI + 0.5 % Pluronic F-68 (Sigma P-5556), pH 7.4 (with HCI) buffer. The compounds of this invention, 10 mM in DMSO, were diluted with DMSO to eight half log concentrations, for example: 1200 pM, 40() ~M, 120 pM, 40 ~M, 12 ~tM, 4 ~tM, 1 ~tM
tS and 0.4 pM. Four concentrations were chosen, then 5 ~I of each were diluted to a total assay volume of 200 X11. The final compound concentrations in the assay, according to the above example, were 30 p.M, 10 ~M, 3 ~tM, 1 pM, 0.3 ~M, 0.1 ~tM, 0.03 p.M and 0.01 pM, respectively. The substrate S-2444 was used at 200 pM in the assay.
Several vials were reconstituted as directed on the vial, aliquoted and stored frozen. The enzyme was 20 further diluted in assay buffer and 10 ~tl was used in the assay. Enzyme concentration in the assay was 2-3 nM. The assay was performed as follows: 175 pL of buffer was pipetted into the polystyrene plate, 5 ~L solution of a compound of this invention in DMSO was added, the mixture was vortexed, 10 ~L of enzyme in buffer was added, the mixture was vortexed, i 0 ~tL of substrate in water was added, the mixture was vortexed, 25 and the plate was placed in a Spectromax ~ (Molecular Devices Corporation, Sunnyvale, Ca) plate reader to follow the course of the reaction for 15 min at 405 nm.
The Spectromax ~ calculated the reaction rates which were used to calculate percent inhibition of the compounds of this invention versus the reaction rate of the enzyme in the absence of any inhibitor. The Ki 's of the inhibitors were calculated from the percent inhibition and 3U previously established Km. The compounds of this invention inhibit urokinase as shown by the data for representative examples in Table 1.
Ta 1 1 Inhibitory Potency of Representative Compounds Against Urokinase SUBSTITUTE SHEET (RULE 26) Exam Ie ICSp (~,M) 1 6.6 I

2 9.8 4 p,$

2.5 6 2.3 3.5 0.1 I.l 3.2 14 0.33 2.5 16 0.03 I ~ 4.26 1 ~ 0.42 19 2.21 0.803 21 I .7 22 1.7 23 4.0 24 4.9 2.1 26 0.04 2~ 0.93 2~ 2.1 2'~ 2.5 3.6 SUBSTITUTE SHEET (RULE 28) WO 99105fl96 PCTIIJS98/15386 31 2.93 I

32 4.6 33 2.4 34 3.5 35 3.97 36 1.75 37 2.34 6.35 39 12.2 40 0.31 41 2.38 42 2.08 43 2.2 44 0. 3 5 45 2.94 46 2.4 47 4.8 4~ 1.3 49 3.3 5() 6.13 51 4.7 52 4.7 53 2.96 54 2.7 55 0.9 56 2.9 57 3.4 5~ 2.53 59 0.41 SUBSTITUTE SHEET (RULE 26) 60 0.72 61 0.73 62 0.64 __ , 63 0.37 64 0.56 65 0.54 66 3. I 3 67 2.78 68 1.74 69 1.38 70 2.57 71 2.39 72 4.30 73 3.3 74 I .61 75 2.09 76 0.96 77 0.23 78 3.57 7'~ 0.96 80 ! .93 81 3.21 82 3.08 83 2.24 84 10.0 85 1.38 86 3.6 I 87 0.63 88 2.73 SUBSTITUTE SHEET (RULE 26) WO_ 99105096 PCTIUS98/I5386, 9 6.5 90 0.07 91 0.05 92 0.04 g 3 2.36 95 1.73 9 6 0.86 97 1.31 9 8 0.24 9 9 3.02 100 3.16 1 01 0.8 1 02 0.34 1 03 0.57 104 1.2 1 05 0.84 1 06 0.76 1 a7 2.34 1 08 0.996 1 09 2.85 111 4.17 1 1 2 0.45 1 1 3 0.403 1 1 4 0.344 1 1 5 0.063 SUBSTITUTE SHEET (RULE 26) 1 1 6 0.045 1 1 7 0.278 1 1 8 0.121 1 1 9 4.41 1 20 0.93 1 21 0.89 1 22 0.33 1 23 1 .24 124 0.12 1 25 0.23 1 26 0.87 1 27 0.085 1 29 4.84 131 4.18 132 O.g6 1 33 0.044 1 34 0.064 1 35 1 .91 1 36 1 .67 1 37 0.82 1 38 0.46 1 39 2.64 1 40 0.46 141 0.00117 i 42 0.54 1 43 0.36 SU6STITUTE SHEET (RULE 26) 1 44 1 .26 I
I

1 45 2.59 1 46 0.372 147 0.213 148 O,g1 149 3,g 150 0.16 1 52 0.083 153 0,877 1 54 0.035 1 55 2.33 156 0,1g 157 3.12 158 O,Og 1 59 2.23 1 60 2.62 1 61 1 .59 1 62 1 .33 1 63 0.03 1 64 0.45 165 0.00068 1 66 0.002 1 67 0.052 1 68 0.003 1 70 0.695 >30 SUBSTITUTE SHEET (RULE 26) 1 74 0.1 7 1 76 S.Oi 1 1 77 14.9 1 79 1 .61 1 80 0.097 1 81 8.92 i 82 >30 1 84 0.375 185 3.19 1 86 2.98 1 87 0.61 3 1 88 0.22 i 89 1 .3 i 90 0.565 1 91 0.887 1 92 1 .6 1 93 0.85 1 94 0.56 1 95 1 .3 1 96 0.62 1 97 2.03 1 98 0.504 1 99 2.3 200 0.037 201 0.077 202 0.792 SUBSTITUTE SHEET (RULE 26) 203 0.624 204 0.331 205 0.337 206 5.73 207 4,12 208 0.96 209 0.82 21 0 0.78 21 1 0.072 212 5.09 213 4,5g 21 4 2.559 215 1.1 21 6 >30 21 7 0.67 21 8 0.086 219 0.103 220 0.03 221 0.52 222 0.346 223 0.07 224 1 .773 225 0.1 04 226 >30 227 0.015 228 0.025 SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCT/US98/15386 229 0.1 17 230 0.1 03 231 0.015 232 0.123 Pharmaceutical Compositions The present invention also provides pharmaceutical compositions which comprise compounds of the present invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions may be specially formulated for oral administration in solid or liquid form, for parenteral injection or for rectal administration.
The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally , intracisternally, intravaginally, intraperitoneally or In topically (such as powders, ointments or drops), bucally or as an oral or nasal spray. The term "parenteral" administration, as used herein, refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion.
Pharmaceutical compositions of this invention for parenteral injection comprise 15 pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diIuents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), and suitable mixtures thereof, vegetable oils (such as olive 20 oilj and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be 25 ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable SUBSTITUTE SHEET (RULE 26) pharmaceutical form may be brought about by the inclusion of agents (such as aluminum monostearate and gelatin) which delay absorption .
In some cases, in order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be s accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form.
Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.
11) lnjectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoestersj and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in ~ 5 liposomes or microemulsions which are compatible with body tissues.
The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use.
20 Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, s sucrose and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, e;alcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate;
e) solution retarding agents such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol rnonostearate; h) absorbents such as kaolin and bentonite clay and i) lubricants such as talc, calcium stearate, 30 magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.
Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCTIUS98115386 The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition such that they release the active ingredients) only, or preferentially, in a certain part of the intestinal tract, optionally or in delayed fashion.
Examples of embedding compositions which can be used include polymeric substances and waxes.
The active compounds may also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients.
Liquid dosage forms for oral administration include pharmaceutically acceptable 1u emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, 15 castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and mixtures thereof.
Besides inert diluents, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents.
Suspensions, in addition to the active compounds, may contain suspending agents such as 2o ethoxylated isostearyl aicohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth and mixtures thereof.
Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or e:arriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room 25 temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.
Compounds of the present invention can also be administered in the form of liposomes.
As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals which 3a are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are the phospholipids and the phosphatidyl cholines (lecithins), both natural and synthetic. Methods to form liposomes are SUBSTITUTE SHEET (RULE 26) known in the art, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (197b), p. 33 et seq.
Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers or propellants which may be required. Opthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of this invention.
Actual dosage levels of active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active compounds) that is effective to ! o achieve the desired therapeutic response for a particular patient, compositions, and mode of administration. The selected dosage level will depend upon the activity of the particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the compound at levels lower than required for to achieve the desired ! 5 therapeutic effect and to gradually increase the dosage until the desired effect is achieved.
Generally dosage levels of about 1 to about 50, more preferably of about 5 to about 20 mg, of active compound per kilogram of body weight per day when administered orally to a mammalian patient. If desired, the effective daily dose may be divided into multiple doses for purposes of administration, e.g. two to four separate doses per day.
Preparation of Compounds of this Invention The compounds of this invention may be prepared by a variety of synthetic routes.
Representative procedures are outlined in the following Schemes 1-6.
'S Abbreviations Abbreviations which have been used in the descriptions of the schemes and the examples that follow are: THF for tetrahydrofuran; DMF for N,N-dimethylformamide; OEt2 for diethyl ether; EDC for 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; NMM
for N-methylmorpholine; LDA for lithium diisopropylamide; TFA for trifluoroacetic acid;
DMSO for dimethylsulfoxide; DMAP for 4-(N,N-dimethylamino)pyridine; HATU for O-(azabenzotriazole-1-yl)-N,N,N',N'-tetramethyluroniumhexafluorophosphate; Boc for tert-butylcarbonyioxy; DDQ for 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; Bn for benzyl; DPPA
for diphenylphosphoryl azide; DCC for dicyclohexylcarbodiimide; EDC for 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; SEM for 2-SUBSTITUTE SHEET (RULE 26) (trimethylsilyl)ethoxymethyl ; dppf for l,1'-bis(diphenylphosphino)ferrocene;
and dba for dibenzylideneacetone. Starting materials, reagents and solvents were purchased from Aldrich Chemical Company (Milwaukee, Wi).
As shown in Scheme 1, naphthalenecarbonitriles 4, 5_ and fi were prepared by treating 3-cyanopropionaldehyde diethyl acetal 2 with a strong base such as lithium diisopropylamide then treating the resulring anion with the appropriately substituted benzaldehyde I_ followed by cyclization and aromatization of the corresponding cyanohydrins ~ with a Lewis acid such as sulfuric acid.
t0 hem I
C C OH
B ~ CHO H CO~CN B ~ CN
~'3 A ~ OCH3 A ~ OCH3 A, B and C are hydrogen and -LARA, -L~RB, -L~R~
-LA-, -LB- and -L~- are -O-RA, R~ and R~ are alkyl C
B ~ ~ CN
A
4: A is hydrogen; B and C are OCH3 5: A, B and C are OCH3 f~: A and B are OCH3, and C is hydrogen t5 As shown in Scheme 2, selective demethylation of 4 with a Lewis acid such as A1CI3 or BBr3, preferably AlCl3, provided 7. 7 was treated with a base such as potassium carbonate, sodium hydride or cesium fluoride followed by RC-X, wherein X is a leaving group, to provide SUBSTITUTE SHEET (RULE 26) X (-L~- is -O-). Alternatively, treatment of 7 with trifluoromethanesulfonic anhydride or I,I,I-trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide provided 9 which may Rc-B, ~ ~ B, be treated with Rc-B(OH)2, O , Rc-I, or R~ ~ wherein Rc is unsubstituted or substituted aryl or heterocycle, in the presence of a palladium catalyst, S preferably Pd(II)C12(dba) or Pd(Ph3P)4, and base, preferably cesium fluoride or potassium carbonate, to provide 10. Alternatively, 9 may be treated with R~-NR 1 R2, wherein R~ is unsubstituted or substituted aryl or heterocycle, and at least one of R1 or R~
is hydrogen, in the presence of a strong base, such as potassium t-butoxide, and a catalyst, such as Pd(II)C12(dba), to provide 1 I.
Scheme 2 OH LcRc \ ~ CN HsC ~ ~ ~ CN

H / / ~ H / /
7 $
OTf LcRc H3C I ~ ~ CN H3C ~ ~ ~ CN
H / / ~ H / /
y R~ is unsubstituted or substituted aryl or heterocycie 10: -L~- is a covalent bond 1 I : -L~- is -NR1_ iS As shown in Scheme 3, selective O-triflation of 12 followed by protection of the amino group of the resulting 13 with acid-labile carbobenzlyoxy provided 14.
Conversion of _14 to _15 was achieved with KCN in the presence of a palladium catalyst, preferably SUBSTITUTE SHEET (RULE 26) tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct, and deprotection of,~ to provide 16 was accomplished with acid, preferably 30~1e HBr in acetic acid. Treatment of 15 with acylating agents R~C(O)Cl and base, preferably triethylamine, diisopropylethylamine or potassium carbonate provided intermediate 17.
S
Scheme 3 NH2 NH2 NHCbz NHCbz / \ OH \ \ OTf / \ OTf / \ CN
12 13 14 1~
NH2. HBr ~cRc / \ CN / \ CN
\ / ~ \ I /
16 l -L~- is -C(O)NRI- or -OC(O)NR~- and R~ is unsubstituted or substituted alkyl, alkeneyl, hererocycle or aryl 1~~ As shown in Scheme 4, selective demethylation of the 8-methoxy group of 18 with a Lewis acid such as AlCl3 or BBr3, preferably AICl3, was followed by reprotection of phenol 19 by alkylation with Bn-X, wherein X is Cl, Br or I, in the presence of a base such as potassium carbonate, sodium hydride or cesium t7uoride. 2() was prepared by deprotonation of this intermediate with a strong, non-nucleophilic base swh as lithium, sodium or potassium n diisopropylamide or alkoxide followed by treatment with an alkyl formate, preferably ethyl formate to provide enol 2(l. Treatment of 20 with hydroxylamine provided isoxazole 21 which may be opened with lithium, sodium or potassium alkoxide, preferably sodium methoxide, to provide 22. Carbonyl reduction with concomitant alkene formation with achieved with sodium borohydride to provide 23; and aromatization with DDQ and catalytic debenzylation with 2U hydrogen and a palladium catalyst, preferably palladium on carbon, provided 24. 24 was SUBSTITUTE SHEET (RULE 26) alkylated by treatment with a base such as potassium carbonate, sodium hydride or cesium fluoride followed by treatment R~-X.
~heme 4 ~cRcO OH O C O OH C O-;
\ -."~ I \ ~ I \ / _~ I \
A / A / A / A /
Ik 19 20 21 A is -LARA, and C is -L~R~, wherein C is -L~R~, wherein L~ is -O- and -LA- and -L~- are -O- and RA is alkyl R~ is arylalkyl C O C OH
\ C~ , \ \ C ~ ~ \ \ CN
A A / A / /
'2 23 24 A is -LARA, wherein -LA- is -O- and RA is alkyl As shown in Scheme 5, monohydrolysis of 25 with one equivalent of base such as lithium, sodium or potassium hydroxide provided the acid-ester 2-fi. Treatment of 2fi with m thionyl chloride or oxalyl chloride/DMF followed by treatment with ammonia provided amide 27. Treatment of 27 with a dehydrating agent such as thionyl chloride or phosphorus oxychloride provided nitrile 2lS.
Regioselec;tive nitration of 2H with nitric acid/potassium nitrate followed by reduction of the vitro group with a palladium catalyst, preferably palladium on carbon, provided intermediate t 5 31, which was treated with R~C(O)Cl or R~OC(O)Cl and base, preferably diisopropylethylamine or potassium carbonate, to provide 37.
Hydrolysis of 2K with one equivalent of lithium, sodium or potassium hydroxide to form carboxylic acid 29 followed by treatment with DPPA or thionyl chloride then sodium azide and hydrolysis of the intermediate isocyanate 32 with acid, preferably sulfuric acid, provided 2o amine 33. Alternatively, treatment of 32 with a primary or secondary amine provided urea 34 SUBSTITUTE SHEET (RULE 26) (-LA- =-NR~C(X)R~-, wherein X is O).
2~ may be coupled to primary or secondary amines, and 33 may be coupled to carboxylic acids to form amides 35 and 36, respectively. In either case, the amines and carboxylic acids are coupled using a dehydrating agent such as DCC, EDC or HATLI.
Scheme 5 \ \ C02C~ ( \ \ C02~ I \ \ CONH2 \ \ CN [ \ \ CN , \ \ CN
RALA / / ~ O2C / / -' RALA / /

-LA-is a covalent bond and R~ is alkoxycarbonyl \ \ CN \ \ CN
--O=C=N / / I
RA LA
3? _34 CN
\ \
RADA / / I \ \ CN

SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTlUS98/15386 LcRC
~ CN
/ /
RALA
-L~- is -C(X)NR1- or -OC(O)NRI- and RC is unsubstituted or substituted alkyl, alkeneyl, hererocycle or aryl;
XisO
CN
29 --~
Rata, -LA- is -NR1C(X)_ wherein X is O
CN

/
RA LA

-LA- is -C(X}NR1-wherein X is O
S As shown in Scheme 6, intermediates wherein -LA- is -C---C- or -C=C- were prepared by treatment of of 38 with a triflaring agent, preferably- t1-ifluoromethanesulfonyl anhydride, to form 39 followed by coupling of the appropriate substituted alkenes or unsubstituted or substituted alkynes using a palladium catalyst, preferably palladium (II) acetate, to form 4U.

SUBSTITUTE SHEET (RUE.E 26) Sch m \ \ CN \ \ CN I \ \ CN
/ /
HO / / Tf0 / / RAt_A

S
As shown in Scheme 7, conversion of the nitrite intermediates to the carboximidamide urokinase inhibitors 41 was achieved by three methods: (1) treatment of the intermediate carbonitriles with a non-nucleophilic base such as lithium, sodium or potassium bis(trimethylsilylamide), preferably lithium bis(trimethylsilylamide} followed by hydrolysis tc~ with acid, preferably HCI; (2) treatment of the nitrite with acid, preferably HCI, followed by treatment with ammonium acetate; and (3) treatment of the nitrite with H2S
followed by treatment with ammonia gas in methanol. Of the three methods, the H2S/NH3/methanol method is preferred. The compounds of the invention were precipitated as hydrochloride or methane sulfonate salts or were purified by reversed phase medium pressure chromatography to form 15 mono- or bis- trifluoroacetate salts.
Scheme 7 C C NH
\ \ CN g ~ \ \ NH2 / / ~ A / /

Synthetic Methods The foregoing may be better understood by reference to the following examples which illustrate the methods by which the compounds of the invention may be prepared and are not intended to limit the scope of the invention as defined in the appended claims.

Example 1 SUBSTITUTE SHEET (RULE 26) 7 8-Dimethoxy-2-nanhthalenecarboximidamide mono(trifluoroacetate) a~
Exam lp a 1 A
7. 8-Dimethoxy-2-narJhthalenecarbonitrile A solution of freshly prepared LDA in THF at -78 °C was treated dropwise with 3-cyanopropionaldehyde diethyl acetal (3.0 g) in THF (5 mL), stirred for 1 h, treated with 2,3-dimethoxybenzaldehyde (3.2 g) in THF (5 mL), warmed to room temperature over 90 min, treated with water (40 mL), concentrated and extracted with chloroform. The organic layer was washed with brine, dried (MgS04) and concentrated to provide 1.5 g of a yellow oil.
tU MS (DCI/NH3) m/e 341 (M+H20)+.
A solution of the oil in methanol (5 mL) was added dropwise to 20% aqueous sulfuric acid ( 100 mL) at 90 °C. The solution was heated for 90 min, cooled to room temperature and extracted with chloroform. The combined organic extracts are washed with brine, dried {MgS04) and concentrated to provide I.0 g of a brown solid which was purified by flash a 5 chromatography on silica gel with 3:1 hexane/ethyl acetate to provide 800 mg of the title compound.
MS (DCI/NH3) m/e 231 (M+H20)+.
Example 1 B
20 7.8-Dimethoxv-2-naphthalenecarboximidamide monoltrifluoroacetatel salt A solution of Example 1 (200 mg) in THF (5 mL) at 0 °C was treated with lithium bis(trimethyisilylamide) (1.0 M in hexane, I.1 mL), stirred for 18 h at room temperature, treated with 10% HCl ( 10 mL), stirred for 24 h at room temperature, concentrated and purified by medium pressure liquid chromatography on a 30 cm x 2 cm C-18 column (40 micron, J.T
25 Baker) with UV detection at 250 nM with solvent mixtures in a gradient ranging from 90%A
(0.1 % aq TFA)/lO~loB (methanol) to 10%A/90%B over 160 min at a flow rate of 5 mL/min (fractions were collected every 2 min for i00 min and analyzed by TLC (10:1:1 acetonitrile/water/acetic acid) for product) to provide 100 mg of the title compound.
tH NMR (300 MHz, DMSO-d6} 8 4.41 {s, 3H), 4.62 (s, 3H), 7.41 (d, 1H), 7.43 (dd, 1H), 30 7.60 (d, 1 H}, 7.80 (d, 1 H), 8.49 (d, 1 H), 9.31 (bs, ZH), 9.48 (bs, 2H);
MS (DCI/NH3) m/e 231 (M+H)+.
Anal. calcd for C13H14N2O2~TFA: C, 52.33; H, 4.39; N, 8.14. Found: C, 51.91;
H, 4.35; N, 8.05.

SUBSTITUTE SHEET (RULE 26) Exam 6. 7. 8-trimethoxy-2-naphthalenecarboximidamid monoftrifluoroacetatel salt Example 2A
6. 7. 8-trimethoxv-2-nat~hthalenecarbonitrile The title compound was prepared as described in Example 1 A but substituting 2, 3, 4-trimethoxybenzaldehyde for 2, 3-trimethoxybenzaldehyde.
MS (DCIlNH3) m/e 261 (M+H20)+.
W Exam In a 2B
6. 7. 8-trimethoxy-2-nat~hthalenecarboximidamide mono(trifluoroacetate) Salt The title compound was prepared and purified as described in Example 1B to provide 100 mg of the title compound.
~H NMR (DMSO-d6, 300 MHz) S 3.9I (s, 3H), 3.98 (s, 3H), 4.06 (s, 3H), 7.36 (s, IH), 1s 7.75 (dd, 1 H) 7.99 (d, 1 H), 8.49 (d, 1 H), 9.18 (bs, 2H), 9.38 (bs, 2H);
MS (DCI/NH3) m/e 261 (M+H)+.
Anal. catcd for C~4H16N203~TFA: C, 51.34; H, 4.58; N, 7.48. Found: C, 50.91;
H, 4.25; N, 7.35.
Ex m 1 fi 7-dimethoxv-2-na~hthalenecarboximidamide monoftrifluoroacetate salt Example 3A
fi~7-dimethox -2-naphthalenecarbonitrile 25 The title compound was prepared as described in Example 1 A but substituting 3,4-dimethoxybenzaldehyde for 2, 3-dimethoxy-benzaldehyde to provide 1.3 g of the title compound.
MS (DCI/NH3) m/e 231 (M+H20)+.
Example 3B
6. 7-dimethoxv-2-naohthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared and purified as described in Example 1 B to provide 100 mg of the title compound.

SUBSTITUTE SHEET (RULE 26) 1H NMR (DMSO-d~,, 300 MHz) 8 3.92 (s, 3H), 3.94 (s, 3H), 7.41 (s, 1H), 7.44 (s, 1H), 7.69 (dd, 1H), 7.93 (d, 1H), 8.49 (d, 1H), 9.18 (bs, 2H), 9.38 (bs, 2H);
MS (DCI/NH3) m/e 231 (M+H)+.
Anal. calcd for C13H14N2O2~TFA: C, 52.33; H, 4.39; N 8.14. Found: C, 52.15; H, 4.20; N
8.10.
Example 4 2-f (7-Aminoiminomethvl-2-methox -~phthalenyl)oxylacetamide mono(trifluoroacetate) salt m Example 4A
7-Methoxv-R-hydroxvnaphthalene-2-carbonitriIe A solution of Example 1 A ( 1 g) in methylene chloride ( 100 mL) at 0 °C was treated with A1CI3, stirred for 4 h at 0 °C and at room temperature for I 8 h, poured into water (200 mL) containing 6N HCl (20 mL), stirred for I h and diluted with methylene chloride (100 mL). The t5 layers were separated, and the organic layer was washed with brine and dried (MgS04) to provide 81 U mg of the title compound as an off-white solid.
MS (DCI/NH3) m/e 217 (M+H20)+.
Example 4B
20 1 Ll-Dimethvlethvl 2-I(7-Cvano-2-methoxv-1-naphthalenyl)oxylacetate A slurry Example 4A (100 mg), K2C03 (70 mg), t-butyl bromoacetate ( 120 mgj and tetrabutylammonium iodide (25 mg) in DMF (3 mL) was stirred for 18 h at room temperature, diluted with water (20 mL) and extracted with ethyl acetate. The organic extract was washed with saturated NaHC03 and brine, dried (Na2S04) and concentrated to provide 25 200 mg of the title compound as a clear oil.
MS (DCI/NH3j m/e 331 (M+H~O)+.
Example 4C
21(7-Aminoiminomethvl-2-methoxv-1-naphthalenyl)oxviacetamide mono(trifluoroacetatel salt 30 Example 4B ( 100 mg) in methanol (S mL) at 0 °C was treated with HCl(g), stirred for 18 h at room temperature and concentrated to provide an off-white solid. The solid was treated with 2N NH3 in methanol (10 mL), heated at 50 °C for 3.5 h, cooled and concentrated to a yellow solid which was purified as described in Example 1 B to provide 10 mg of the title compound.

SUBSTITUTE SHEET (RULE 26) 1H NMR (300 MHz, DMSO-d6) 8 3.93 (s, 3H), 4.79 (s, 2H), 7.55 (d, 2H), 7.65 (dd, 1H), 7.72 (d, 1 H}, 7.85 (d, 1 H), 8.09 (d, 1 H), 8.7 (d, I H), 9.03 (bs, 2H), 9.45 (bs, 2H);
MS (DCI/NH3) m/e 2?4 (M+H)+.
Anal. calcd for Ct4H15N303'TFA: C, 49.62; H, 4.16; N, 10.85. Found: C, 49.33;
H, 4.03;
s N, 10.50.
Example 5 7-Benzvloxv-8-iodo-2-naohthalenecarboximidamide mono(trifiuoroacetate) salt 1o Example SA
7-Benzvloxy-8-iodo-2-naphthalenecarbonitrile The title compound was prepared as described in Example 43A but substituting benzyl bromide for propyl iodide.
MS (DCI/NH3) m/e 403 (M+NH4}+.
15 Example SB
7-Benzvloxv-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example SA according to the procedure of Example I B.
1H NMR (300 MHz, DMSO-d6) 8 9.30 (br, 4H}, 8.44 {s, 1H), 8.I2 (d, IH), 7.71 (d, 2H), 20 7.67 (dd, 1 H), 7.57 (d, 2H), 7.45-7.34 (m, 3H), 5.45 (s, 2H);
MS (DCI/NH3) m/e 403 (M+H)+.
Anal. calcd for C~gH15N~0I~TFA: C, 46.53; H, 3.12; N, 5.43. Found: C; 46.55;
H, 3.10; N, 5.19.
'-5 Example 6 Methvl I(7-aminoiminomethvI-2-methox -y 1-naphthalen I)oxylacetate mono(trifluoroacetate) salt Example 6A
30 Methvl f(7-cvano-2-methoxv-1-naphthalen 1 oxviacetate A solution of Example 4A (600 mg), Cs2C03 (500 mg), t-butyl bromoacetate (120 mg}
and tetrabutylammonium iodide (2S mg) in DMF ( I S mL) was stirred for 18 h at room temperature, diluted with water (20 mL) and extracted with ethyl acetate. The organic extract SU9STiTUTE SHEET (RULE 26) WO 99!05096 PCT/US98J15386 was washed with saturated NaHC03 and brine, dried (Na2S04) and concentrated to provide 800 mg of the title compound as a clear oil.
MS (DCI/NH3) m/e 331 (M+H20)+.
Example 6B, Methyl f(7-aminoiminomethvl-2-methoxy-1-naphthalen~rllox~rlacetate mono(trifluoroacetate~
Example 6A (100 mg) in methanol (30 mL) at 0 °C was treated with HCI(g), stirred for 18 h at room temperature and concentrated to provide an off-white solid. The solid was treated ~0 with ammonium acetate (100 mg) in methanol (10 mL), heated at 40 °C
for 15 h, cooled and concentrated to a yellow solid which was purified as described in Example IB
to providel0 mg of the title compound.
I H NMR (300 MHz, DMSO-d6) 8 3.65 (s, 3H), 3.93 (s, 3H}, 4.79 (s, 2H), 7.65 (dd, 1 H), 7.72 (d, 1 H}, 7.85 (d, I H), 8.09 (d, 1 H), 8.7 (d, 1 H), 9.03 (bs, 2H), ~ 5 9.45 (bs, 2H);
MS (DCI/NH3) m/e 289 (M+H)+.
Anal. calcd for C~SHt6N204~TFA: C> 50.75; H, 4.26; N, 6.96. Found: C, 50.42;
H, 4.03; N, 6.77.
20 Exam lie 7.
f(7-aminoiminomethvl-2-methox -~-naphthaien Iv )oxvlacetic acid mono~trifluoroacetatel salt A solution of Example 6B ( 100 mg) and LiOH~HzO ( I 50 mg) in 1: I THF/H20 ( I
0 mL) at 5 °C was stirred 45 min and concentrated to provide an off-white solid. The solid was dissolved in 1 N HCl (20 mL), stirred 48 h at room temperature and filtered.
The resulting ?5 white solid was purified as described in Example 1B to provide 20 mg of the title compound.
~ H NMR (300 MHz, DMSO-d~) 8 3.93 (s, 3H), 4.79 (s, 2H), 7.65 (dd, 1 H), 7.72 (d, I H), 7.85 (d, IH), 8.09 (d, 1H), 8.7 (d, 1H), 9.23 (bs> 2H), 9.45 (bs, ZH);
MS (DCI/NH3) m/e 275 (M+H)+.
Anal. calcd for C~4H14N204~TFA: C, 49.49; H, 3.89; N, 7.21. Found: C, 47.53;
H, 3.71; N, ~0 6.83.
Example 8 N-f4-(Aminomethvl)~henvll-6-aminoiminomethyl-2-nanhthalenecarboxamide bis~trifluoroacetate) salt SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCT/US9811538ø
Examlhe ~A
2 6-Nanhthalenedicarboxvlic acid monomethvl ester A suspension of dimethyl 2, 6-naphthalenedicarboxylic acid (39.b g, 162 mmole) in dioxane (1.20 L) was heated at 70-80 °C until all solid dissolved, slowly treated with 1 equivalent of KOH in methanol, stirred for additional 30 minutes at 70 °C, cooled to room temperature, filtered and washed with dioxane and diethyl ether, dissolved in water, treated with 1 N HCl until the aqueous layer was acidic to pH paper, filtered, washed with water and dried under vacuum to provide 33 g of a white powder.
MS (DCI/NH3} m/e 231 (M+H)+.
Example 8B
6-(Chlorocarbonvl)-2-naphthalenecarboxylic acid methyl ester A suspension of Example 8A ( 15 g> 65 mmole) in toluene ( 190 mL) was treated with t 5 thionyl chloride (20 mL, 276 mmole) then DMAP ( 15 mg), heated at reflux for 1 h and heated at 85 °C for an additional 35 min. The condenser was replaced with a distilling head and 60 mL
of solvent was removed. The thick precipitate which formed while cooling to room temperature was triturated with hexane and filtered to provide 14.8 g of white solid.
MS (DCI/NH3) m/e 249 (M+H)+.
Example 8C
6-(Aminocarbonvll-2-naphthalenecarboxylic acid meth l~r A solution of Example 8B ( 15 g, 60.3 mmole) in methylene chloride (400 mL) at room temperature was treated with dry ammonia gas to precipitate the product. The mixture was stirred for an additional 15 min and filtered. The solid was washed with water and dried under vacuum to yield 13.3 g of a white powder.
MS (DCI/NH3) m/e 230 (M+H)+.
Example 8D
6-Cvano-2-naphthalenecarboxvlic acid meth 1 a tPr A suspension of Example 8C (31 g, 135 mmole) in trimethyl phosphate (450 mL) was treated with triphosgene (27 g, 136 mmole), stirred for 20 min at room temperature and heated in an oil bath at 80 °C for 1 h. The product precipated from the solution while cooling to room SUBSTITUTE SHEET (RULE 26) temperature. The thick slurry was treated with water and fettered, and the white solid was thoroughly washed with water and dried under vacuum to provide 26.3 g of the title compound.
MS (DCI/NH3) m/e 212 (M+H)+.
E~ple E
6-Cyano-2-nanhthaienecarboxylic acid Example SD (1.9 g, 9 mmole) in 1:1 THF/H20 (40 mL) was treated with LiOH~H20 ( 1.9 g, 45 mmole), stirred 90 min at room temperature and concentrated to a thick slurry. The slurry was dissolved in water (20 mL), acidified to pH 2 with solid citric acid and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2S04) and concentrated to provide 1.6 g of the title compound as a white solid.
MS (DCI/NH3) m/e 197 (M+H)+.
Exam lie 8F
tert-Butoxvcarbonvlamino-4-aminomethylaniline 4-Aminomethylaniline (2 g) in 2:1 THF/H20 (30 mL) was treated with Boc anhydride (3.93 g), stirred at room temperature for 18 h, diluted with water and concentrated to white slurry. The slurry was dissolved in ethyl acetate, washed with water and brine, dried (Na2S04) and concentrated to provide 2.4 g of a yellow solid.
MS (DCI/NH3) m/e 223 (M+H)+.
Exam~he AG
N-14-(aminomethyllphen 1~-cyano-2-naphthalenecarboxamide A solution of Example 8E (200 mg) and hunig's base (180 ~L) in DMF (S mL) at 5 °C
?a was treated with HATU ( 193 mg), stirred for 1 h at 5 °C, treated with Example 8F (120 mg) and diisopropylethylamine ( 100 ~tL) in DMF (5 mL), stirred for 8 h at room temperature, diluted with ethyl acetate ( 10() mL), washed sequentially with 1 N H3P04, saturated sodium bicarbonate and brine, dried (Na2S04) and concentrated to provide a yellow oil which was purified on silica gel with 1 % methanol/methylene chloride to provide 200 mg of the title compound.
MS (DCI/NH3) m/e 419 (M+H20)+.
Example 8H

SUBSTITUTE SHEET (RULE 26) WO 99105096 PCTIUS98/1538k N-f4-(aminomethvl) henvll-6-aminoininomethyl-2-nanhthalenecarboxamide bis(trifluoroacetatel salt The title compound was prepared from Example 8G (200 mg) by the procedure and purification from Example SB to provide 37 mg of the title compound.
S tH NMR (300 MHz, DMSO-d6) b 4.08 (m, 2H), 7.45 (d, 2H), 7.88 (d, 2H), 7.95 (dd, 1H), 8. I 8 (dd,1 H), 8.20 (bs, 3H), 8.23 {d, l H), 8.35 (d, l H), 8.58 (s, l H), 8.70 (s, 1 H), 9.39 (s, 2H), 9.55 (s, 2H), 10.68 (s, IH);
MS (DCI/NH3) m/e 319 (M+H)+.
Anal. calcd for C19H17N40~TFA: C, 50.56; H, 3.69; N, 10.25; Found: C, 50.18;
H, 3.59; N, ttj 10.11.
Exam 1~ 9 N-f4-(amino)phenvll-6-aminoiminometh 1-2-naphthalenecarboxamide bis(trifluoroacetate) salt t5 Exam In a 9A
N-f4-(amino)phenyll-6-cvano-2-naphthalenecarboxamide The title compound was prepared according to the procedure described for Example 8G
but substituting 1,4-diaminobenzene for Example 8F. MS (DCI/NH3) m/e 288 (M+H)+.
Example 9B
N-f4-(amino)nhenvll-6-aminoiminomethyt-2-naphthalenecarboxamide bis(trifluoroacetatel salt The title compound was prepared with Example 9A ( 100 mg) following the procedure and purification from Example 6B.
tH NMR (300 MHz, DMSO-d~,) ~ 7.15 (d, 2H), 7.75 (d, 2H), 7.95 (dd, 1H), 8.18 (dd, 1H), ?5 8.23 (d, 1 H), 8.35 (d, 1 H), 8.58 (s, 1 H), 8.70 (s, 1 H), 9.25 (s, 2H), 9.48 (s, 2H), 10.58 (s, 1 H);
MS (DCI/NH3) m/e 305 (M+H)+.
Anal. calcd for ClgH~6Nq.0~2TFA: C, 49.63; H, 3.41; N, 10.52; Found: C, 46.57;
H, 3.62;
N, 10.66.
Example 10 1-f(7-Aminoiminomethvl-2-methoxy-I-naphthalenvlloxyl-3-hydroxwro ane mono(trifluoroacetatel salt SUBSTITUTE SHEET (RULE 26) Exam I
I-f(7-Cvano-2-methoxv-1-nanhthalen Iloxvl-3-lf2-tetrahvdro-2H-pyranviloxy~pro ane monoltrifluoroacetatel salt A suspension of Example 4A (200 mgj and Cs2C03 (0.32 g) in DMF (15 mL) was treated with 2-(3-bromopropyl)-tetrahydro-2H-pyran (0.25 g), stirred at room temperature for 18 h then diluted with water ( 100 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with 10% citric acid, water and brine, dried (MgS04) and concentrated to provide 320 mg of an oil.
MS (DCI/NH3) m/e 323 (M+H)+.
lU
Example 10B
1-1l7-Aminoiminomethyl-2-methox -~ hthalenyllox r~l-~-hydrox ro~ne monoltrifluoroacetate) salt Example l0A {0.3 g} was processed and purified according to the procedure of Example 1i IB to provide 110 mg of an off-white solid.
~H NMR (300 MHz, DMSO-d~) 8 1.97 (q, 2H), 3.67 (t, 2H), 4.2t) (t, 2H), 7.61-7.70 (m, 3H), 7.84 (d, l H), 8.08 (d, 1 H), 8.50 (d, 1 H);
MS (DCI/NH3) m/e 275 (M+H)+.
Anal. caIcd for C13H13N302~TFA~0.75H20: C, 50.81; H, 5.14; N, 6.97. Found: C, SI.23;
2U H, 5.28; N, 6.97.
Exam l~e l I
8-amino-2-naphthalenecarbonitrile h~drobromide 25 Example 11 A
2-Trifluoromethanesulfo~loxx-8-aminonaphthelene A solution of 8-amino-2-naphthol (10 g) and triethylamine (12 mL) in dioxane (200 mL) was treated with N-phenyltrifluoromethane sulfonimide (25 g) in dioxane (80 mL), stirred for 4 h and concentrated. The resulting dark brown solid was triturated with hexane and filtered to 3U provide 12 g of the title compound as a brown solid.
MS (DCI/NH3) m/e 292 (M+H)+.
>~xamnle 1 I B
2-Trifluoromethanesulfon~y-8-carbonylben~yloxyaminonanhthelene SUBSTITUTE SHEET (RULE 26) A solution of Example I 1 A (2 g) in I 0% aq Na2C03 (20 mL) and dioxane (250 mL) was treated with benzylchloroformate (2 mL) in dioxane (20 mL), stirred at room temperature for 5 h then extracted with ethyl acetate. The organic layer was dried (MgS04) and concentrated, and the crude product was chromatographed on silica gel with 7:
I hexane/ethyl acetate to provide 2.5 g (86%) of the title compound.
MS (DCI/NH3) m/e 443 (M+NH4)+_ Example I 1 C
8-lN-carbonvlbenzy~x )-2-nanhthalenecarbonitrile Tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct ( 120 mg), I,1'-bis(diphenyfphosphino)-ferrocene (260 mg), potassium cyanide (766 mg), Example 1 IB (2.5 g) and N-methyl-2-pyrrolidione (5 mL) were combined sequentially, stirred at room temperature until a yellow reaction complex formed then warmed to 80 °C for 40 min.
The dark brown reaction mixture was cooled to room temperature and chromatographed on I~ silica gel with 9:1 hexane/ethyl acetate to provide I.5 g of the title compound as a colorless solid.
MS (DCI/NH3) m/e 292 (M+NH4)+.
Example 1 l D
$-Amino-2-naphthalenecarbonitrile hydrobromide Example 1 I C ( 1.4 g) was treated with a solution of 30% HBr in acetic acid (5 mL) and stirred at room temperature for 6 h. The reaction mixture was treated with diethyl ether and filtered to provide I.I g of the title compound as a yellow solid.
MS (DCI/NH3) m/e 186 (M+NH4)+.
?5 Example 12 General Acviation Procedure A suspension of Example l OD { 1 equivalent), triethylamine ( 1 equivalent) and DMAP
(0.25 equivalents) in methylene chloride (0.3M) was treated dropwise with the appropriate acid 3c) chloride ( 1.1 equivalents) in methylene chloride (0.3 M), stirred at room temperature for 30 min and treated with water (SO mL). The organic layer was dried (MgS04), concentrated and used in following reactions without further purification.
Example I3 SUBSTITUTE SHEET (RULE 26) General Amidine ~nthesis Procedure A solution of crude acylation products from Example 12 (ca. 100 mg) at room temperature in 10:1 pyridineariethylamine ( 10 mL) was treated with hydrogen sulfide for 5 min, stirred at room temperature for 18 h, diluted with water (50 mL) and extracted with ethyl acetate. The ethyl acetate was dried (MgS04) and concentrated. The residue was dissolved in acetone (30 mL), treated with methyl iodide (2 mL), refluxed for 1 hour, evaporated to dryness, redissolved in methanol (25 mL), treated with ammonium acetate (100 mg), stirred for 18 h at room temperature, concentrated and purified as described in Example 1 B to provide Examples 14-20 as white solids.
Exam l~ a 14 8-(carbonvlbenzvloxy)amino-2-naphthalenecarboximidamide mono(trifluoroacetate),sal I H NMR (DMSO-d~, 300 MHz) 8 5.14 (s, 2H), 7.36-7.50 (m, SH}, 7.67-7.90 (m, 4H), 8.14 (d, 1 H), 8.67 (s, 1 H), 9.08 (s, 2H), 9.37 (s, 2H), 9.78 (s, 1H);
t, MS (DCI/NH3) m/e 320 (M+H)+.
Anal. calcd for C19HISN302~1.STFA~O.SH20: C, 52.91; H, 3.94; N, 8.41. Found:
C, 52.86;
H, 4.07; N, 8.18.
Example I S
N-f7-(aminoiminomethvl)-1-naphthalenvl)acetamide mono(trifluoroacetate) salt I H NMR (DMSO-d6, 300 MHz) 8 4.19 (s, 3H), 7.66-7.88 (m, 3H), 8.12-8.16 (m, 2H), 8.69 (s, 1 H), 8.98 (d, 1 H), 9.16 (s, 2H), 9.47 (s, 2H), 10.14 (s, I H);
MS (DCI/NH3) m/e 228 (M+H)+.
Anal. calcd for C14H12N30~1.2TFA~().25H20: C, 50.18; H, 4.02; N, 11.40. Found:
C, ?s 50.62; H, 4.47; N, 10.90.
Example 16 Methvl f7-(aminoiminometh 1)-Y~1-n_aphthalenvl)carbamate mono(trifluoroacetate) salt IH NMR (DMSO-d6, 300 MHz) 8 3.88 (s, 3H), 7.67-7.85 (m, 4H), 8.14 (d, 1H), 8.6 (s, I H), 8.28 (s, 3H), 9.67 (s, I H);
MS (DCI/NH3) m/e 244 (M+H)+.
Anal. calcd for C13H13N302~TFA: C,50.43; H, 3.95; N, 11.76. Found: C, 50.12;
H, 4.05;
N, I 1.61.

SUBSTITUTE SHEET (RULE 26) Example 17 Methy_1~j7-(aminoiminomethyl)-1-na hthalenyllaminol-3-oxo r~oyonate monoltrifluoroacetate) alt 1H NMR (DMSO-d6, 300 MHz) 8 3.69 (s, 2H), 3.71 (s, 3H), 7.69 (m, 4H), 8.18 {d, 1H), 8.58 (s, 1 H), 9.11 (s, 2H), 9.48 (s, 2H);
MS (DCI/NH3) m/e 286 (M+H)+.
Anal. calcd for C15H14N3O3~I.1TFA~H20: C, 48.18; H, 4.26; N, 9.80. Found: C, 48.30; H, 4.09; N, 9.58.
o Exam lp a 18 N-f7-(aminoiminomethvl)-1-naphthalenvll-2-(phenvlmethoxy~acetamide monoltrifluoroacetate_) S L
l H NMR (DMSO-d6, 300 MHz) 8 4.29 (s, 2H)> 4.73 (s, 2H), 7.33-7.48 (m, SH), 7.69 (m, 4H), 8.17 (d> 1 H}, 8.47 (s, 1 H), 9.21 (br, 4H), I 0.0 (s, 1 H);
MS (DCIlNH3) m/e 334 (M+H)+.
Anal. caIcd for C2pH1gN302~1TFA~H20: C, 56.77; H, 4.76; N, 9.03. Found: C, 56.84; H, 4.49; N, 8.93.
Example 19 N-f7-(aminoiminomethyl)-1-naphthalenvll-1 3-benzodioxole-5-carboxamide mono(trifluoroacetatel salt ~ H NMR (DMSO-d6, 300 MHz) b 6.19 ( 1 H, 2H), 7.12 (d, 1 H), 7.65-7.79 (m, SH), 7.97 (d, 1 H), 8.20 (s, 1 H), 8.53 (s, 1 H), 9.2 (br s, 3H), zs 10.35 (s, 2H);
MS (DCI/NH3) m/e 334 (M+H)+.
Anal. calcd for C~gH14N302~TFA: C, 55.82; H, 3.68; N, 9.30. Found: C, 55.69;
H, 33.61;
N, 9.23.
Examl 1~ a 20 N-17-(aminoiminomethvl)-1-nanhthalenvllbenzenemethanewlfonamide mono(trifluoroacetate) 1H NMR (DMSO-d6, 300 MHz) 8 4.60 (s, 2H), 7.32-7.33 (m, SH), 7.67-7.70 (m, 2H), 7.82 (d, l H), 7.92 (d, I H), 8.17 (s, 1 H), 8.70 (s, 1 H), SUBSTITUTE SHEET (RULE 26) 9.14 (s, 2H), 9.35 (s, ZH), 9. I 9 (s, I H);
MS (DCI/NH3) m/e 340 (M+H)+.
Anal. calcd for C~gH17N302S~TFA~H20: C, 50.95; H, 4.28; N, 8.91; Found: C, 50.76; H, 3.70; N, 8.65.
Example 21 I-f (7-aminoiminomethvl-2-methoxy-I-nanhthalenyl)oxyl-~-bromopro mono(h~drochloride) salt 1o Exam In a 21A
I-f(7-Cvano-2-methoxv-1-naphthalenyl)oxy -'~-bromopronane mono(hvdrochloridel salt The title compound was prepared from Example 4A, 1,3-dibromopropane and the procedure of Example 10A.
MS (DCI/NH3) m/e 337 (M+NH4)+.
Example 21B
1-f(7-Aminoiminomethyl-2-method-I-na~hthalenyl oxyl-3-bromoRropane mono(hydrochloride) salt The title compound was prepared from Example 21 A and the procedure of Example 1 B.
After HCl hydrolysis, the solution was cooled to 0 °C, and the white solid which precipitated was filtered and dried to provide the title compound.
1 H NMR (300 MHz, DMSO-d6) 8 2.35 (m, 2H), 3.86 (t, 2H), 4.00 (s, 3H), 4.25 (t, 2H), 7.65 (dd, 1 H), 7.70 (d, 1 H), 7.90 (d, 1 H), 8.10 (d, 1 H), 8.55 (s, i H), 9.
IS (br s, 2H), 9.42 (br s, 2H);
MS (DCI/NH3) m/e 337 (M+H)+.
Anal. calcd for C~SHI~BrN202~HC1~0.75H20: C, 46.53; H, 5.08; N, 7.23. Found:
C, 46.65;
H, 5.11; N, 7.16.
Example 22 3U 3-f(7-Aminoiminomethvl-2-methoxv-1-na hty halenylloxy ronene monoltrifluoroacetate, salt Ex mlhe 22A
3-f(7-Cvano-2-methox -v 1-nanhthalenyl oxylpro~ nee SUBSTITUTE SHEET (RULE 26) The title compound was obtained as a biproduct from the procedure of Example 21A.
MS (DCI/NH3) m/e 257 {M+NH4)+.
Example 22B
3-1(7-Aminoiminomethyl-2-methox -y I-na hthalenylloxylpr~;nene mono(trifiuoroacetatPl salt The title compound was prepared from Example 22A and the procedure and purification in Example 1 B.
1H NMR (300 MHz, DMSO-d6) 8 4.00 (s, 3H}, 4.70 (d, 2H), 5.22 (d, 1H), 5.42 (d, 1H), 6.18 (m, 1 H), 7.62 (dd, I H), 7.85 (d, I H), 8.10 (d, 1 H), 8.50 (s, 1 H), 9.12 (br s, 2H), 9.45 l0 (br s, 2H);
MS (DCI/NH3) m/e 257 (M+H)+.
Anal. calcd for C~SH16N2~2'TFA-0.25H20: C, 54.47; H, 4.71; N, 7.47. Found: C, 54.61;
H, 4.38; N, 7.40.
l5 Exams 1~ a 23 1-1(7-Aminoiminomethvl-2-methoxy-1-naphthalen 1~)oxyl-3-phenyl,propane mono(hydrochioride) salt Exam 1~ 23A
2U 1-f(7-Cyano-2-methoxy-1-naphthalenyl)oxyl-3-ohen~propane The title compound was prepared from Example 4A, 1-bromo-3-phenylpropane, and the procedure of Example 10A.
MS (DCI/NH3) m/e 335 (M+NH4)+.
25 Exam lie 23B
1-1~7-Aminoiminomethvf-2-methoxy-1-naphthaie~l)oxyl-3=phenylpropane monolhvdrochloride) salt The title compound was prepared from Example 23A and the procedure of Example 21 B.
30 ~ H NMR (300 MHz, CD30D) 8 2.21 (m, 2H), 2.94 (t, 2H), 4.00 (s, 3H), 4.22 (t, 2H), 7.18 {m, 1 H), 7.28 (m, 4H), 7.62 (m, 2H), 7.79 (d, 1 H), 8.02 (d, 1 H), 8.62 (s, 1 H);
MS (DCI/NH3} m/e 335 (M+H)+.
HRMS (FAB) calcd m/e for C21H23N202'HCI: 335.1760 (M+H)+. Found m/e 335.1762.

SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCT/US98/15386 Exam! 1~ a 24 I-fl7-Aminoiminomethyl-2-methox -v I-na~hthalenvl)oxyl-3-f I-!3 4 dimethox~ henyllpropane monolhydrochloride) salt Example 24A
I-Bromo-3-l3.4-dimetho~~hen~pro ane The title compound was prepared from 3-(3,4-dimethoxyphenyl}-1-propanol as described in Journal of the American Chemical Society, 95 , 8749 ( 1973), which is incorporated herein by reference, to provide the title compound.
W MS (DCI/NH3) m/e 276 (M+NI-I4)+.
Example 24B
1-l!7-Cvano-2-methoxv-1-nanhthalen lv loxvl-3-ll-(3 4-dimethoxy~phenyl ro ane The title compound was prepared from Examples 4A and 24A and the procedure of l S Example 10A.
MS (DCI/NH3) m/e 395 (M+NH4)+.
Exam I
!-Il7-Aminoiminomethvl-2-methoxy-1-naphthalen~l)oxvl-3-( 1-!3 4-20 dimethoxv)phenYlll~r~ane monolh~drochloride) salt The title compound was prepared from Example 24B and the procedure of Example 21B.
~ H NMR (300 MHz, DMSO-d6) 8 2.11 (m, 2H), 2.80 (t, 2H), 3.74 (s, 6H), 3.98 (s, 3H), 4.15 (t, 2H), 6.75-6.92 (m, 3H), 7.65 (dd, 1 H), 7.70 (d, I H), 7.86 (d, 1 H), 8.10 (d, 1 H}, 25 R.55 (s, 1H), 9.15 (br s, 2H), 9.53 (br s, 2H) ;
MS (DCI/NH~) m/e 395 (M+H}+.
Anal. calcd for C23H26N204~HC1O).SH20: C, 62.79; H, 6.42; N, 6.37. Found: C, 63.08; H, 6.38; N, 6.17.
3O Examl I~ a 25 7-Methoxv-R-!2-furanvl)-2-naDhthalenecarborimidamide monoltrifluoroacetate~
salt Exam lie 25A
7 _Methoxv-li-trifluoromethanes Ifonvloxy-2-narzhthaIenecarbonitrile SUBSTITUTE SHEET (RULE 26) A solution of Example 4A (310 mg) in methylene chloride (5 mL) at 0 °C
was treated with I ,1,1-trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyljmethanesulfonamide (614 mg) and triethylamine (240 mL), stirred for 18 h at room temperature, diluted with methylene chloride ( 100 mL), washed with water and 20% aq NaOH, dried (MgS04) and concentrated to provide 560 mg of the title compound as a white solid.
MS (DCI) m/e 349 (M+H20}+.
Exam l Furan-2-boronic acid ir) A solution of furan (5.3 mL, 73 mmole) in diethyl ether (67 mL) at -20 °C was treated with n-butyllithium (2.5 M in hexanes, 26 mL, 65 mmole), stirred for 2 hours at -20 °C and transferred by cannula to a -20 °C solution of triisopropyl borate (33 mL, 147 mmole) in diethyl ether (17 mL). The thick mixture was warmed to room temperature, treated with 3N HCl (200 mL) and extracted with diethyl ether. The extracts were washed with 1N KOH, and the KOH
t5 layer was cooled to 0 °C and acidified with 6N HCI. The acidic solution was extracted with diethyl ether, and the acidic ether extracts were washed with brine, dried (MgS04) and concentrated to provide the title compound.
1 H NMR (300 MHz, DMSO-d6) 8 6.45 (dd, 1 H), 7.05 (t, 1 H), 7.80 (dd, 1 H), 8.19 (s, 2H).
Exam In a 25C
7-Methoxv-R-(2-furanyi)-2-naphthalenecarbonitrile Example 25A ( 1. l0 mmol) was combined with Pd(OAc)2 (0.1 1 mmol) and I, l' bis(diphenylphosphino)ferrocene (0.22 mmol) in DMF {5 mL,), stirred for 10 min, treated with Example 25B ( I .32 mmol) and Cs2C03 (3.3 mmol), heated at $5 °C for 6 h, cooled to room temperature arid chromatographed on silica gel with l0~lo ethyl acetate/hexane to provide the title compound.
MS (DCI/NH3) m/e 250 (M+H}+.
Exam 1e~25D
8-(2-Furanvl)-7-methoxv-2-naphthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 25C and the procedure and purification in Example 1 B.

SUBSTITUTE SHEET (RULE 26) t H NMR (300 MHz, DMSO-d6) 8 3.97 (s> 3H), 6.73 (m, 1 H), 6.80 (m, I H), 7.64 (dd, 1 H), 7.78 (d, 1H), 7.91 (m, IH), 8.16 (d, 1H), 8.20 (d, 1H), 8.30 (s, IH), 9.08 (br s, 2H), 9.40 (br s, 2H);
MS (DCI/NH3) m/e 267 (M+H)+.
Anal. calcd for C16H14N202~TFA: C, 56.85; H, 3.98; N, 7.37. Found: C, 56.68;
H, 3.67; N, 7.35.
Example 26 methyl 6-(aminoiminomethvl)-4-f (methoxvcarbonyllaminol-2-naphthalenecarboxylate 1o mono(trifluoroacetate) salt Example 26A
2-Cvano-1-nitro-6-carboxynaphthalene methyl ester A solution of 2-cyano-6-methylnaphthoate (5.2 g) in concentrated sufuric acid (75 mL) 1 S at 0 °C was treated with potassium nitrate ( 1.03 ed) in one portion, stirred for 10 min, poured onto ice (500 g) and extracted with ethyl acetate. The ethyl acetate layer was washed with water, 1 N NaOH and brine, dried (MgS04), treated with silica gel and filtered.
Concentration of the ethyl acetate to ca. 200 mL precipitated the product. The mixture was heated until all solid dissolved, treated with MeOH (20 mL) and ether (20 mL) and stirred overnight.
The resulting 2t) solid was filtered and washed with methanol to provide 2.31 g of the title compound as a cream-colored solid. The mother liqueuor was evaporated, treated with methylene chloride (250 mL) then solid silica gel, filtered and concentrated. Crystalization from ethyl acetate/methanol provided an additional 1.6 g of product for a total yield:
3.91 g (62%).
MS (DC1/NH~) m/e 257 (M+H)+.

Example 26B
2-Cvano-1-amino-6-carboxynaphthalene methyl ester A solution of Example 26A (lg, 3.9mmole) and 10% Pd on carbon (112 mg) in ethyl acetate (80 mL) was stirred under 1 atm of hydrogen for 9 h, purged with nitrogen for 1 h, 30 filtered and evaporated to provide 810 mg (92%) of the title compound as a yellow solid.
MS (DCI/NH3) m/e 227 (M+NH4)+.
Example 26C
6-Cvano-4-f(methoxvcarbonyl)aminol-2-naphthalenecarboxylic acid methyl ester SUBSTITUTE SKEET (RULE 26j A solution of Example 26B (2.50 mmol) in methylene chloride (40 mL) was treated sequentially with diisopropylethylamine (2 mL) and methylchloroformate (195 ~L, 2.52 mmole), stirred for 2 h, treated with methanol { 10 mL), stirred for an additional 10 minutes, diluted with methylene chloride (60 mL), washed with water and brine, dried (MgS04) and evaporated. The residue was purified on silica gel using 10% ethyl acetate/hexane to provide 280 mg (59%) of light yellow solid.
MS (DCI/NH3) m/e 285 (M+H)+.
Example 26D
t0 Methyl 6-(aminoiminomethyl)-4-1(methoxy arbonyl)amino]-2-naphthalenecarboxvlate mono(,~,rifluoroacetate) salt The title compound was prepared using Example 26C ( 125 mg, 0.44 mmol) and the procedure in Example 40D to provide 35mg of a white solid.
tH NMR (DMSO-d~,) 8 3.7R (s, 3H), 3.95 (s, 3H), 7.R9 (dd, 1H), 8.37-R.40 (m, 3H), 8.53 t 5 (s, 1 H), 8.740 (s, 1 H) 9.18 (br s, 2H), 9.45 (br s, 2H), 9.90 (s, 1 H), 8.42 (s, 1 H), 8.63 (d, 1 H), 9.18 (br s, 4H), 10.58 (s, 1H);
MS (DCI/NH3) m/e 302 (M+H)+.
Anal. calcd for C15HI5N304~TFA~1.SH20: C, 46.16; H, 4.33; N, 9.50. Found: C, 45.96;
46.16; H, 4.06; N, 9.12.
Example 27 (E)-17-Methoxv-R-f2-lPhenyl)ethenyll l-2-naphthaleneimidamide mono(trifluoroacetate) salt Example 27A
LE)-(7-Methoxv-R-f2-(Phenyl)ethenyll l-2-nat~hthalenecarbonitrile Example 25A and styrene boronic ester, prepared according to the procedure of Journal of the American Chemical Society, ~ 5249 ( 1975), which is incorporated herein by reference, was processed according to the procedure described in Example 26B to provide the title compound.
MS (DCI/NH3) m/e 303 (M+NH4)+.
ExamnIe 27B
(E)-17-Methoxv-R-f2-(Phenyl)ethenvll l-2-naphthaleneimidamide mono(trifluoroacetatel salt The title compound was prepared from Example 27A and the procedure of Example 1B.

SUBSTITUTE SHEET (RULE 26) 1H NMR (300 MHz, DMSO-d6) 8 3.98 (s, 3H), 7.28 (t, 2H), 7.39 (t, 2H), 7.64 (m, SH), 8.00 (d, 1 H), 8.10 (d, 1 H), 8.62 (s, 1 H), 9.22 (br s, 2H), 9.42 (br s, 2H};
MS (DCI/NH3) m!e 303 (M+H)+.
Anal. calcd for C2pH1gN20~TFA: C, 63.46; H, 4.60; N, 6.73. Found: C, 63.10; H, 4.73; N, 6.43.
Example 28 6-(4-Phenvlbutynyl)-2-nanhthalenecarboximidamide mono(trifluoroacetate) salt Example 28A
6-Hvdrox -~naphthalenecarbonitrile A solution of 6-bromo-2-naphthol (25.0 g, 112 mmol) and copper(I) cyanide ( 11 g, 123 mmol) in DMF (30 mL) was heated at 135 °C for 18 h, cooled, diluted with ethyl acetate (50 mL), triturated with 10% aq sodium hydroxide and filtered through Celite~. The filtrate was 2S acidified to pH 2 and extracted with ethyl acetate. The combined extracts were concentrated, dissolved in ethanol ( 150 mL) and triturated with water to precipitate 14.01 g of the title compound.
MS (DCI/NH3) m/e 170 (M+H)+.
2t) Example 28B
6-(Trifluoromethanesulfonyloxv)-2-naphthalenecarbonitrile A solution of Example 28A (14.01 g, 82.8 mmol) and triethylamine (9.2 g, 91.1 mmol) in methylene chloride (40 mL} at 0 °C was treated dropwise with trifluoromethylsulfonic anhydride (28 g, 99.4 mmol), warmed to 25 °C for 48 h, concentrated, redissolved in ethanol 25 (50 mL) and triturated with water to precipitate 8.4 g of the title compound.
MS (DCI/NH3) m/e 319 (M+NH4)+.
Example 28C
6-(4-Phenvlbutvnvl)-2-na~hthalenecarbonitrile 30 The title compound was prepared from Example 28B, 4-phenyl-1-butyne and the procedure of Example 57B.
MS (DCI/NH3) m/e 299 (M+NH4)+.
Example 28D

SUBSTITUTE SHEET (RULE 26) 6-(4-Phenvlbutvnvl)-2-nanhthalenecarbQximidamide mono(trifluoroace~ tel alt The title compound was prepared from Example 28C and the procedure of Example 1B.
1H NMR (300 MHz, DMSO-d6) 8 2.80 (t, 2H), 2.95 (t, 2H), 7.22 (m, 1H), 7.36 (m, 4H), 7.58 {d, 1H), 7.82 (d, 1H), 8.05 (d, 1H), 8.10 (d, 2H), 8.45 (s, 1H), 9.10 (br s, 2H), 9.42 (br s, 2H);
MS (DCI/NH3) m/e 299 (M+H)+.
Anal. calcd for C2lHigN2~TFA~0.75H20: C, 64.86; H, 4.85; N, 6.58. Found: C, 64.78; H, 4.64; N, 6.03.
to Examp]e 29 7-(2-Hvdroxvethoxvl-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt Example 29A
3-II(1.1-Dimethvlethvl)dimethvlsilyl ~xyl-1-propano( 4-nitrobenzenesulfonate is A solution of 3-t-butlydimethylsiloxy-I-propanol, prepared by the method of McDougal, et al. JOC, 1986, 51, 3388, which is incorporated herein by reference, (7.6 g, 40 mmol) and diisopropylethylamine (10.4 mL, 60 mmol} in methylene chloride (200.
mL) at 0 °C
was treated with p-nitrophenylsulfonyl chloride (9.7 g, 44 mmol), stirred for 3 h, poured into saturated NaHC03 and exacted with diethyl ether. The extracts were washed with brine, dried 20 (Na2S04), and concentrated. The residue was chromatographed on silica gel with 5% ethyl acetate/hexanes to provide 6.00 g of the title compound.
MS (DCI/NH3) m/e 395 (M+NH4)+.
Example 29B
25 7-12-fl(1.I-Dimethviethvlldimethylsilylloxylethoxyl-8-iodo-2-naphthalenecarbonitriIe The title compound was prepared in a manner analogous to that of Example 43A
but substituting Example 29A for propyl iodide.
MS (DCl/NH3) m/e 468 (M+H)+.
3o Example 29C
7-(2-Hvdroxvethoxy)-8-iodo-2-nat~hthalenecarbonitrile The title compound was prepared in a manner analogous to that of Example 53F
but substituting Example 29B for Example 53E.
MS (DCI/NH3) m/e 357 (M+H)+.

SUBSTITUTE SHEET (RULE 26) Exam 1~9D
7-l2-Hvdroxvethoxvl-8-iodo-2-narzhthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 29B according to the procedure of Example 1 B.
t H NMR (300 MHz, DMSO-d6) 8 1.96 (m, 2H), 3.69 (t, ZH), 4.33 (t, 2H), 4.58 {br, I H), 7.63 (d, 1 H), 7.66 (dd, 1 H}, 8.12 {dd, 2H), 8.42 (s, 1 H), 9.20 (s, 2H), 9.53 (s, 2H);
MS (DCI/NH3) m/e 245 (M+H)+;
Anal. calcd for Ct3H12N202I~TFA~0.21H20: C, 53.07; H, 4.85; N, 7.74.
i0 Found: C, 53.07; H, 4.75; N, 7.65.
Exam 1R a 30 7-(2-Hvdroxvethoxv)-2-naDhthalenecarboximidamide monoftrifluoroacetate) salt Example 30A_ 7-(2-Hvdroxyethoxy)-2-n~yhthalenecarbonitrile Example 29B ( I20 mg, 0.26 mmol), palladium(II)Cl2dppf (46 mg, 0.03 mmol) and diisopropylamine (263 mg, 2.6 mmol) were heated in a sealed tube for 2 h at I00 °C, cooled to room temperature, diluted with ethyl acetate, washed with water, dried (Na2S04), and 2o concentrated. The residue was purified on silica gel with 15% ethyl acetate/hexanes to provide 85 mg of the title compound.
MS (DCI/NH3) m/e 342 (M+H)~.
Example OB
7-(2-Hvdroxvethox )-y 2-na hn thalenecarboximidamide mono(trifluoroacetate) salt 2S The title compound was prepared from Example 29B according to the procedure of Example 1 B.
~ H NMR (300 MHz, DMSO-d6) 8 1.96 (m, 2H}, 3.69 (t, 2H}, 4.33 (t, 2H), 4.58 (br, 1 H), 7.63 (d, 1 H), 7.66 (dd, 1 H), 8.12 (dd, 2H}, 8.42 (s, 1 H), 9.20 (s, 2H), 9.53 (s, 2H);
MS (DCI/NH3) m/e 228 (M+H)+;
3o Anal. calcd for Ct4H15N202~TFA: C, 53.78; H, 4.51; N, 7.84.
Found: C, 53.60; H, 4.30; N, 7.81.
Exam le 1 6-(4-Methvl-1-Dentvnvl)-2-nanhthalenecarboximidamide monoltriflunrnace~tel cair SUBSTITUTE SHEET (RULE 26) exam lp a 31 A
6-l4-Methvl-1-pen nyll-2-nanhthalenecarbonitrile The title compound was obtained from Example 28B, 4-methyl-I-pentyne and the procedure of Example 57B.
MS (DCI/NH3) m/e 251 (M+NH4)+.
Exam Ip a 31 B, 6-(4-Methvl-1-Dentynvl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt to The title compound was prepared from Example 3IA and the procedure of Example IB.
~H NMR (300 MHz, DMSO-d6) 8 1.05 (d, 6H), 1.90 (m, 1H), 2.2U (d, 2H}, 7.62 (dd, 1H), 7.82 (dd, 1 H), 8.09 (d, 1 H), 8.12 (d, 1 H), 8.18 (s, 1 H), 8.48 (s, 1 H}, 9.12 (br s, 2H), 9.42 (br s, 2H);
MS (DCI/NH3) rn/e 251 (M+H)+.
1S Anal. calcd for Cl~HtgN2~TFA: C, 62.63; H, 5.26; N, 7.69. Found: C, 64.85;
H, 5.32; N, 7.46.
Example 32 6-l5-Phenvlpentvnvl)-2-naphthalenecarboximidamide monoftrifluoroacetate) salt Example 32A
6-f 5-Phenylpentynyl)-2-naphthalenecarbonitrile The title compound was obtained from Example 28B, 5-phenyl-I-pentyne and the procedure of Example 57B.
MS (DCI/NH3) m/e 313 (M+Nl-I4}+.
Example 32B
6-(5-Phenvhentvnvl)-2-nanhthalenecarboximidamide mono(trifluoroacetate) Salt The title compound was prepared from Example 32A and the procedure of Example IB.
3u ~ H NMR (300 MHz, DMSO-d6) 8 I .90 (m, 2H), 2.80 (t, 2H), 3.39 (t, 2H), 7.19-7.37 (m, SH), 7.62 (dd, IH), 7.82 {dd, 1H), 8.08 (d, 1H), 8.15 (d, IH), 8.18 {s, I H), 8.48 (s, 1 H), 9.15-9.45 (br d, 4H);
MS (DCI/NH3) m/e 313 (M+H)+.

SUBSTITUTE SKEET (RULE 26) Anal. calcd for C22H20N2~'1'FA: C, 67.60; H, 4.96: N, 6.57. Found: C, 67.32;
H, 5.21; N, 6.27.
Example 33 6-(3-Phenvl-1-Droovnvl)-2-naphthalenecarboximidamide monoltrifluoroacetate) salt Example 33A
6-(3-Phenyl-1-p~vnyl)-2-n ~hthalenecarbonitrile The title compound was obtained from Example 28B, 3-phenyl-1-propyne and the procedure of Example 57B.
MS (DCI/NH3) m/e 285 (M+NH4)+.
Example 33B
6-(3-Phenyl-1-propvnyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt 5 The title compound was prepared from Example 33A and the procedure of Example 5B.
~H NMR (300 MHz, DMSO-d~,) 84.00 (s, 2H), 7.28-7.50 (m, 5H), 7.70 (dd, 1H), 7.85 (dd, 1 H), 8.09 (d, 1 H), 8.15 (d, 1 H), 8.21 (s, 1 H), 8.49 (s, 1 H), 9.21 (br s, 2H), 9.45 (br s, 2H);
MS (DCI/NH3) m/e 285 (M+H)+.
Anal. calcd for C2pH 16N2~TFA~0.25H20: C, 65.59; H, 4.38; N, 6.95. Found: C, 65.43; H, 3.95; N, 6.70.
Example 34 6-(Phenvlethynyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt 'S Example 34A
6-(Phenyleth~nyl)-2-naphthalenecarbonitrile The title compound was obtained from Example 28B, phenylacetylene and the procedure of Example 57B. MS (DCI/NH3) m/e 271 (M+NH4)+.
Example 34B
6-(Phenvlethvnvl)-2-navhthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 34A and the procedure of Example 1 B.
~ H NMR (300 MHz, DMSO-d6) 8 7.49 (t, 3H), 7.62 (m, 2H), 7.80 (dd, 1H), 7.86 (dd, 1 H), 8.15 (d, 1H), 8.19 (d, 1H), 8.38 (s, 1H}, 8.52 (s, 1H), 9.38 (br s, 4H);

SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTlUS98/15386 MS (DCI/NH3) m/e 271 (M+H)+.
Anal. calcd for Ct9Ht4N2~TFA: C, 65.62; H, 3.93; N, 7.29. Found: C, 65.64; H, 4.1 l; N, 7.21.
Exam Ip a 35 3-Amino-N-f3-16-(aminoiminomethyl)-2-naphthalen ly 1-2-propvnyllbenzamide monoftrifluoroacetate) salt Example 35A
6-(3-Amino-1-propynyl -2-naphthalenecarbonitrile The title compound was obtained from Example 28B, propargyl amine and the procedure of Example 41 A.
MS (DCI/NH3) m/e 207 (M+NH4)+.
is Example 35B
3-Amino-N-f 3-(6-cyano-2-naphthalenvl)-2-propynyllbenzamide A solution of Example 35A ( 100 mg, 0.49 mmole), 3-aminobenzoic acid (73 mg, 0.53 mmolej, EDC (141 mg, 0.74 mmole) and DMAP (89mg, 0.74 mmole), in THF (5.5 mL) was stirred at room temperature for 2.5 h and concentrated. The residue was dissolved in methylene chloride, washed with 1 N HCI, water, saturated NaHC03, and brine, dried (MgS04) concentrated and purified by flash chromatography on silica gel with 2%
ethanol/methylene chloride to provide the title compound.
MS (DCI/NH3) m/e 326 (M+H)+.
2S Example 35C
3-Amino-N-f3-f6-(aminoiminometh l~~hthale~ll-2-propynyllbenzamide mono(trifluoroacetate) salt The title compound was prepared from Example 35B and the procedure of Example 1B.
~ H NMR {300 MHz, DMSO-d~,) 8 4.32 (d, 2H), 5.69 (br s, 2H), 6.58 (d, 2H), 7.62 (m, 3H), 7.82 (d, 1 H), 8.08 (d, 1 H), 8.14 (d, 1 H), 8.20 (s, 1 H), 8.43 (s, 1 H), 8.60 (t, 1 H), 9.19 (br s, 2H), 9.42 (br s, 2H);
MS (DCI/NH3) m/e 343 (M+H)+.
Anal. calcd for C2lHtgN40~TFA~0.25H20: C, 59.93; H, 4.26; N, 12.16. Found: C, 59.86;
H, 3.97; N, 11.93.

SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTlUS98/15386 Exam_ lp a 36 4-Amino-N-f3-f6-aminoiminomethyl-2-naphthalenvl)-2-prop~n~vllbenzamide mono(trifluoroacetate) salt Example 36A
4-Amino-N-f3-(6-cyano-2-na hthaleny_112-~lzvn~]~enzamid~
Example 35A and 4-aminobenzoic acid were subjected to the conditions described in Example 35B to afford the title compound.
t0 MS (DCI/NH3) m/e 326 (M+H)+.
Exam le 3 ~B
4-Amino-N-f3-(6-aminoiminomethyl-2-nalahthalenvil-~-prQRynvllbenzamide mono(trifluoroacetate) ,alt I S The title compound was prepared from Example 36A and the procedure of Example SB.
tH NMR (300 MHz, DMSO-d6) 8 4.38 (d, 2H), 6.89 (m, IH), 7.20 (m, 2H), 7.22 (s, 1 H), 7.63 (dd, 1 H), 7.82 (dd, 1 H), 8.09 (d, 1 H), 8.12 (d, 1 H), 8.20 (s, 1 H), 8.46 (s, 1 H), 8.95 (t, 1 H), 9.19 (br s, 2H), 9.42 (br s, 2H);
MS (DCI/NH3) m/e 343 (M+H)+.
2() Anal. calcd for C2tH16N40~2.STFA: C, 49.27; H, 3.19; N, 8.54. Found: C, 49.27; H, 3.33;
N, 8.89.
Exam i~ a 37 (S)-2-Amino-N-f 1-f(6-aminoirtinomethyl-2-naphthalenvl)carbonyllcxcfohexvll~r_opionamide 'S bis(trifiuoroacetate) salt Example 37A
6-ffl-Aminocyclohex lyethynvll-2-naphthalenecarbonitrile The title compound was obtained from Example 28B, 1-ethynylcyclohexylamine and the 30 procedure of Example 41 A.
MS (DCI/NH3) m/e 275 (M+NH4)+.
Exam In a 37B
(S)-2-Amino-N-f 1-f(6-cvano-2-naohthalenyl)carbonyllcyclohexvl~propionamide SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTlUS98/15386 Example 37A and N-(t-butoxycarbonyl)-L-alanine were subjected to the conditions described in Example 35B to provide the title compound.
MS (DCI/NH3) m/e 446 (M+H)+.
S exam le 7 (S)-2-Amino-N-fI-f( -aminoiminomethyl-2-naa hthalenyl~carbonyllc~rclohex ~~11, roRionamide bisltrifluoroacetate) salt The title compound was a rearrangement product of Example 37B resulting from the procedure of Example SB.
t0 tH NMR (300 MHz, DMSO-d~,) b 1.24 (d, 3H), 1.40-1.62 (m, 8H}, 2.15-2.26 (s, IH), 2.29-2.38 {s, IH), 3.51 (d, 1H), 3.78 (d, 1H}, 3.82 (s, 1H), 7.90 (dd, 2H), 8.09 (dd, 1H), 8.18 (d, 1H), 8.37 (d, 1H), 8.55 (s, 1H), 8.78 (s, IH), 9.31 (s, 2H), 9.50 (s, 2H);
MS (DCI/NH3) m/e 381 (M+H)+.
I5 Anal. calcd for C~3H2gN402~2TFA~2H20: C, 49.39: H, 5.22; N, 8.53. Found: C, 49.15; H, 4.79; N, 8.70.
Ex mple 3R
6-methoxv-8-benzvloxv-2-naphthalenecarboximid~mide monoftrifluoroacetate, salt Exam le 8A
8-Hvdroxv-6-methoxy-3 4-dihydro-2H-nanhthalen-1 one A solution of 6, 8-dimethoxy-3, 4-dihydro-2H-naphthalen-I-one (IS g, 72.8 mmole), prepared according to the procedure of J. Chem. Soc., London 2782 (1955), which is incorporated herein by reference, in methylene chloride ( I50 mL) at 0 °C was treated portionwise with AIC13 (14.3 g, 107 mmole), stirred for 20 h at room temperature, poured onto ice with stirring and extracted with methylene chloride when the ice melted.
The extracts were washed with water and brine, dried (MgS04) and concentrated to provide 13.8 g of the title compound.
3~ MS (DCI/NH3) m/e 193 (M+H)~.
Examho a 38B
$-Benzvloxv-6-methoxv-3 4-dihy ro-2H-n phthalen 1 one SUBSTITUTE SHEET (RULE 26) A mixture of Example 38A (2.5 g, 13 mmole), benzyl bromide (2.1 mL, 17.8 mmole), K2C03 powder ( 14.3 g, 100 mmole), and 2-butanone (88 mL) was stirred at reflux for 4 h, treated with additional benzyl bromide ( 1.0 mL, 8.5 mmole), stirred at reflux for an additional 3 h, cooled to room temperature, filtered and concentrated. The residue was dissolved in methylene chloride, washed with 1N HCI, water and brine, dried (MgS04) and concentrated.
The crude product was purified on silica gel with 30% ethyl acetate/hexanes to provide the title compound.
MS (DCI/NH3) m/e 283 (M+H)+.
no Exam Ie~38C
3.4-Dihvdro-2-(hvdroxvmethvlenel-6-methoxy-R-(ohe~lmethoxy) ll2Hl naphthalenone Sodium metal ( 1.29 g, 55.9 mmole) was added portionwise to a mixture of ethanol (4.2 mL} and benzene ( 15 mL). The mixture was stirred at reflux for 1.5 h, cooled to 0 °C and treated dropwise with ethyl formate (5.6 mL, 70 mmole) then dropwise with of a solution of IS Example 3HB (6.7g, 23.8 mmole) in benzene (20 mL), stirred at room temperature for 2 h, cooled to 0 °C, treated sequentially with ice/water and 6N HCl (75 mL) and extracted with ethyl acetate. The extracts were washed with brine, dried (MgS04) and concentrated to provide the title compound.
MS (DCI/NH3} m/e 311 (M+H)+.
Example 38D
4 5-Dihvdro-7-methox ~-~9-(~henvlmethoxy)nanhthf2 1-dlisoxazole f2.1-dlisoxazole A suspension of Example 38C (7.5 g, 24.3 mmole), hydroxylamine hydrochloride (4.11 2S g, 57.6 mmole) and acetic acid (63 mL) was stirred at 1 10 °C for 7 min, cooled to room temperature, diluted with water and extracted with methylene chloride. The extracts were washed with water and brine, dried (MgS04), and concentrated. The crude product was purified by flash chromatography on silica gel with 30% ethyl acetate/hexanes to provide the title compound.
3o MS (DCI/NH3) m/e 308 (M+H)+.
Exam 1 8-Benzvloxv-2-cvano-6-methoxy-3 4-dih dronaphthalen 1 one _77_ SUBSTITUTE SHEET (RULE 26) Sodium methoxide, prepared from sodium metal (0.17 g, 7.35 mmol} in methanol (3.9 mL), was treated dropwise with a solution of Example 38D (I.S g, 4.9 mmole) in benzene (SO
mL), stirred at room temperature for 4.5 h, treated sequentially with water and 1 N HCl and extracted with ethyl acetate. The extracts were washed with brine, dried (MgS04) and concentrated to provide the title compound.
MS (DCI/NH3) m/e 308 (M+H)+.
Example 38F
2-Cvano-6-methoxy-8-Benzyloxv-3 4-dihvdronaphthalene to A suspension of Example 38E (2.6 g, 8.6 mmole) in absolute ethanol (2S mL) at room temperature was treated portionwise with NaBH4 ( 1.6 g), stirred for 20 min at room temperature and for 20 min at reflux, cooled to room temperature, treated with water (20 mL) and concentrated. The residue was dissolved in methylene chloride, washed with water and brine, dried (MgS04), filtered and concentrated to provide 2.6 g of an orange foam. The foam ~5 was stirred at reflux for 20 min with p-toluenesulfonic acid monohydrate (0.52 g, 2.7 mmole) in benzene (52 mL), cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried (MgS04) and concentrated to provide the title compound.
MS (DCI/NH3) m/e 309 (M+NI-14)+.
20 Exam lp a 38G
2-Cyano-6-methoxv-8-benzvloxynar?hthalene A solution of Example 38F (0.4 g, 1.4 mmole), 2,3-dichloro-S,6-dicyano-1,4-benzoquinone (0.79 g, 3.S mmole) in benzene (40 mL) was stirred at reflux for 4 hours, treated with additional 2,3-dichloro-S,6-dicyano-1,4-benzoquinone (0.4 g, 1.8 mmole), stirred at 25 reflux for an additional S h, cooled to room temperature, diluted with ethyl acetate, washed with saturated NaHC03 and brine, dried (MgS04} and concentrated to provide the title compound.
MS (DCI/NH3) m/e 290 (M+H)+.
Example 38H
30 8-Benzvloxv-6-methoxv-2-nanhthalenecarboximidamide monoftrifluoroacetate) alt The title compound was prepared from Example 38G and the procedure of Example I B.
~H NMR (300 MHz, DMSO-d6} 8 4.38 (d, 2H), 6.89 (m, 1H), 7.20 (m, 2H), 7.22 (s, 1H), 7.63 (dd, IH), 7.82 (dd, 1H), 8.09 (d, IH), 8.12 (d, IH), 8.20 (s, IH), 8.46 (s, 1H), 8.95 (t, I H), 9. I9 (br s, 2H), 9.42 (br s, 2H);
_78_ SUBSTITUTE SHEET (RULE 26) MS (DCI/NH3) m/e 307 (M+H)+.
Anal. calcd for CigH1gN202~TFA: C, 60.00; H, 4.56; N, 6.66. Found: C, 59.93;
H, 4.46; N, 6.51.
Example 39 2-f (7-Aminoiminomethvl-3-methoxv-1-naphthale~l)oxvlacetamide mono(trifluoroacetate) salt Example 39A
6-Methoxy-8-hydroxy_2=,na~hthalenecarbonitrile A mixture of Example 38G ( 1.62 g, 5.6 mmole) and 10% dry Pd/C (0.50 g) in methanol ( 150 mL) was hydrogenated in a Pan shaker at room temperature under 4 atm for 30 h. The mixture was filtered and concentrated to provide the title compound.
MS (DCI/NH3) m/e 217 (M+NH4)+.
1 S Example 39B
2-f(7-Cvano-3-methox -1-naphthale~l~)oxylacetamide Example 39A and 2-bromoacetamide were subjected to the conditions described in Example SA to provide the title compound.
MS (DCI/NH3) m/e 274 (M+NH4)+.
Example 39C
2-f(7-Aminoiminomethvl-3-methoxv-1-na~hthalenyl)oxylacetamide mono(trifluoroacetate) salt The title compound was prepared from Example 39B and the procedure of Example 1 B.
~ H NMR (300 MHz, DMSO-d6) 8 3.93 (s, 3H), 4.70 (s, 2H), 6.70 (d, I H), 7.09 (d, 1 H), z5 7.65 (s, 2H), 7.82 (dd, 1H), 7.99 (d, !H), 8.70 (s, 1H), 9.05 (s, 2H), 9.38 (s, 2H);
MS (DCI/NH3) m/e 274 (M+H)+.
Anal. calcd for C~4H15N3O3~TFA: C, 49.62; H, 4.16; N, 10.85. Found: C, 49.68;
H, 4.24;
N, 10.61.
=~~ Example 40 N-(6-aminoiminomethvl-2-nanhthalenyl)-N'-phenylurea mono(trifluoroacetate) salt Example 40A
6-Cvano-2-nanhthalenecarbonyl chloride SUBSTITUTE SHEET (RULE 26) A suspension Example 8E (4.4 g, 22.3 mmol) in toluene (100 mL) was treated with thionyl chloride (6.0 mL) and DMAP (5 mg), heated at 55 °C for lh, treated with additional thionyl chloride (3 mL), warmed to 95 °C for 1 h, cooled to room temperature, stirred in hexane (75 mL) for 2.5 h and fltered to provide 3.62 of the tide compound as a white powder. The filtrate was concentrated and triturated with ether to provide an additional 1.02 g of the title compound.
MS (DCI/NH3) m/e 2I5 (M+H)+.
Example 40B
2-Cvano-6-naRhthoyl azide A solution of Example 40A ( 1.65 g, 7.65 mmole) in acetone (600 mL) at room temperature was treated with a solution of sodium azide (3 g, 46 mmole) in water ( 10 mL), stirred for 1.5 h and diluted with water (60 mL). The resulting solid was filtered, washed with water and dried to provide 4.24 g of the title compound as a white powder.
MS (DCI/NH3) m/e 240 (M+NH4)+.
Example 40C
N-(6-cvano-2-na hthale~i)-N'- henylurea A solution of Example 40B (221.2 mg, 1 mmole) in toluene ( 18 mL) was heated at 85 °C for 1 h then at 95 °C for 1.5 h, cooled to room temperature, treated with aniline (240 ~L, 2.63 mmole), stirred for 25 min and treated with ether ( 10 mL). The resulting solid was collected, washed with ether and dried under vacuum to yield 230 mg of white powder.
MS (DCI/NH3) m/e 305 (M+NH4)+.
Example 40D
N-(6-aminoiminomethvl-2-naphthalenyl)-N,'-phenvlurea mono(trifluoroacetate) salt A solution of Example 40C (148 mg, 0.5 mmole) in 10:1 pyridineariethylamine (10 mL) was treated with H2S for 5 min, stirred at room temperature for 18 h and concentrated.
The resulting solid was dissolved in acetone ( 15 mL), treated with iodomethane (0.8 mL, 12.8 mmole), stirred for 2 h, diluted with ether ( 10 mL), filtered, washed with ether and dried under vacuum. The resulting solid was dissolved in methanol, treated with 2N NH3 in methanol (2 mL), warmed to 50 °C for 4 h and concentrated. The product was purified according to the procedure described in Example 1 B to provide 62 mg of the title compound.
1H NMR (300 MHz, DMSO-d6) S 7.00 (t, IH), 7.31 (dd , 2H), 7.52 (d, 1H), _80_ SUBSTITUTE SHEET (RULE 26j 7.65 (dd, IH), 7.76 (dd, IH, 8.02 (d, 2H), 8.30 (s, IH), 8.39 (s, IH), 9.05 (br s, 2H), 9.11 (s, IH), 9.33 (br s, 2H), 9.42 (s, IH);
MS (DCI/NH3) m/e 305 (M+H)+;
Anal. calcd for C1gH16N40~TFA: C, 57.42; H, 4.10; N, 13.39. Found: C, 57.50;
H, 4.05;
s N, I 3.08.
Exam a 41 (El-6-f2-lPhenvI)ethenvll-2-naphthalenecarboximidamide mono(trifluoroacetate) sal Example 41 A
El-6-I2-(Phenyl)ethenvll-2-na~hthalenecarbonitrile A solution of Example 28B (350 mg, I .16 mmol), styrene ( 157 mg, 1.51 mmol), palladium (II) acetate (26 mg, 0.12 mmol), triphenylphosphine (61 mg, 0.23 mmol), triethylamine (2 mL) and acetonitrile ( I mL) in a sealed tube with minimal head volume was l5 heated at 100 °C for 19 h, diluted with ethyl acetate {20 mL), washed with water, dried (MgS04) and concentrated with silica gel (4 g). The mixture was chromatographed on silica gel with 10% ethyl acetate/hexane to provide 160 mg of the title compound.
MS (DCI/NH3) m/e 273 (M+NH4)+.
Example 41 B
E)-6-f2-(Phenvllethenvll-2-nanhthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 41 A from the procedure of Example I B.
1H NMR (300 MHz, DMSO-d~) 8 7.33 (t, IH), 7.4 (t, 2H), 7.5 (d, 2H), 7.69 (d, IH), 7.70 2~ (d, 1 H), 7.81 (dd, 1 H), 8.03 (dd, 1 H), 8. I 0 (d, 1 H), 8. I 3 (d, 1 H), 8.17 (s, 1 H), 8.44 (s, I H), 8.97 (s, 2H), 9.41 (s, 2H);
MS (DCI/NH3) m/e 273 (M+H)+ ;
Anal. calcd for C~yH~6N2~TFA: C, 65.28; H, 4.43; N, 7.25. Found: C; 64.95; H, 4.60; N, 6.42.
Exam lp a 42 6-I2-lPhenyl)ethvll-2-nanhthalenecarboximidamide mono(trifluoroacetate) salt Example 42A
_81 _ SUBSTITUTE SHEET (RULE 26) 6-f2-lPhenyllethyll-2-naphthalenecarbonitrile A mixture of Example 57B (80 mg, 0.31 mmol) and palladium on carbon (20%
water, 50 mg) in methanol (5 mL) was stirred under 1 atm of hydrogen for 0.5 h, filtered and concentrated to provide 72 mg of the title compound.
S MS (DCI/NH3) m/e 275 (M+NH4)+.
Ex mp e1 42B
6-f2-lPhenvllethvll-2-nanhthalenPC-arboximidamide monoltrifluoroacetate salt The title compound was prepared from Example 42A and the procedure of Example 1B.
t0 IH NMR (300 MHz, DMSO-d6) s 3.03 (m, 2H), 7.23 (m, SH), 7.60 (dd, IH), 7.76 (dd, 1 H), 7.85 (s, 1 H), 8.03 (t, 2H), 8.42 (s, 1 H), 8.99 (s, 2H), 9.39 (s, 2H);
MS (DCI/NH3) m/e 275 (M+H)+.
Anal. calcd for CI9HIgN20~1.33TFA: C, 61.29; H, 4.59; N, 6.61. Found: C;
61.56; H, 4.62;
N, 5.21.
IS
Example 43 7-Pronoxv-R-iodo-2-naphthalenecarboximidamide monoltrifluoroacetate) salt Example 43A
20 7-pro oiL-v-R-iodo-2-naphthalenecarbonitrile Example 53A (65 mg, 0.25 mmol) in DMF (2 mL} was treated with propyl iodide (40 mL), stirred at 65 °C for 1 h, diluted with water and extracted with diethyl ether. The organic extracts were dried (MgSO4) and concentrated, and the residue was purified on silica gel with 10% ethyl acetate/hexanes to provide 160 mg of the title compound.
25 MS (DCI/NH3) m/e 355 (M+H)+.
Exam lie 43B
7-Pronoxv-R-iodo-2-nanhthaienecarboximidamide monoltrifluoroacetat 1 salt The title compound was prepared from the product in Example 43A according to the 30 procedure of Example I B.
I H NMR (300 MHz, DMSO-d6) b 1.09 (t, 3H), 1.82 (m, 2H), 4.23 (t, 2H), 7.62 (d, 1 H), 7.65 (dd, 1 H), 8.12 (dd, 2H), 9.15 (s, 2H), 9.42 (s, 1 H), 9.53 (s, 2H);
MS (DCI/NH3} m/e 355 (M+H)+.

SUBSTITUTE SHEET (RULE 26) Anal. calcd. for C14H15N20I~TFA~0.26C~Hg: C, 43.49; H, 3.70; N, 5.69. Found:
C; 43.50;
H, 3.59; N, 5.75.
Example 44 S ( ~ )- 6-(3-Phenvloxiran lY )-2-naphthalenecarboximidamide mono(trifluoroacetate) salt Example 44A
( ~ )-6-(3-Phen loxiranyl -2-naphthalenecarbonitrile A solution of Example 41 A (69 mg, 0.27 mmol) and m-chIoroperbenzoic acid (70 mg, 0.41 mmol) in methylene chloride (3 mL) was stirred at 25 °C for 3 days, concentrated, loaded on a silica gel column (pretreated with 0.1 % triethylamine in ethyl acetate) and eluted with 10%
ethyl acetate/hexane) to provide 72 mg of the title compound.
MS (DCI/NH3) m/e 289 (M+NH4)+.
Example 44B
{ ~ )- 6-(3-Phenvloxiranyl)-2-naphthaienecarboximidamide mono(trifluoroacetate) salt The title compound was prepared with Example 44A from the procedure of Example 1B.
t H NMR (300 MHz, DMS~-d6) 8 4.24 (d, 1 H), 4.35 (d, 1 H), 7.43 (m, SH), 7.67 (dd, I H), 7.83 (dd, 1 H), 8. I2 (s, 1 H), 8.13 (d, 1 H), 8.16 (d, 1 H), 8.50 (s, I H), 9.03 (s, 2 H), 9.44 (s, 2H);
MS (DCI/NH3) m/e 289 (M+H)+.
Anal. calcd for C~9H16N20~ l.3 TFA: C, 64.52; H, 4.55; N, 6.51. Found: C;
64.35; H, 4.60;
N, 5.87.
Example 45 (E)-6-f 2-(2-Thienyl)ethenyl l-2-n~hthalenecarboximidamide mono(trifluoroacetate) salt 3o Example 45A
2-V inylthiophene A suspension of methyltriphenylphosphonium bromide (19.13 g, 53.5 mmol) in THF
( 100 mL) was treated dropwise with 2M butyllithium in THF ( 17.8 mL) then dropwise with 2-SUBSTITUTE SHEET (RULE 26j carboxythiophene (5 g, 44.6 mmol), stirred for 30 min then distilled at 74-78 °C to provide the title compound.
MS (DCI/NH3) m/e 111 (M+H}+.
Exam 1e~45B
fEl-6-f 2-l2-Thien Ily ethenyll-2-naphthalenecarbonitrile The title compound was prepared from the product of Example 45A and the procedure of Example 41 A.
MS (DCI/NH3) m/e 279 (M+NH3)+.
Ex n Ir~45C' (E)-6-f2-f2-Thienvl)ethenLrll-2-nanhthalene~arh ximidamide mono(trifluoroac .rarPl calr The title compound was prepared from Example 45B and the procedure of Example 1B.
~H-NMR (300 MHz, DMSO-d6) S 7.12 (dd, 2H), 7.15 (d, 1H), 7.32 (d, 1H), 7.6 (d, 1H), 7.74 (d, 1 H), 7.80 (dd, 1 H), 7.9-8.1 (m, 3H), 8.14 (s, 1 H), 8.43 (s, 1 H), 9.03 (s, 2H), 9.42 (s, 2H};
MS (DCI/NH3) m/e 279 (M+H)+;
Anal. calcd. for C1~H14N202S~TFA: C, 53.77; H, 3.56; N, 6.60. Found: C; 54.88;
H, 3.66;
N, 6.45.
Exam_ Ip a 46 -l3-Oxobutvll-2-naphthalenecarboximidamide monoftrifluoroac tate~ salt Example 46A
6-f3-Oxobutvl)-2-naphthalenecarbonitrile The title compound was prepared from Example 28B, 1-buten-3-of and the procedure of Example 41 A.
MS (DCI/NH3) m/e 241 (M+NH4)+.
Exam Il~ a 46B
6-(3-Oxobutvll-2-nat~hthalenec~rboximidami P mono(tri uoroa~etate) salt The title compound was prepared from Example 46A and the procedure of ExamplelB.

SUBSTITUTE SHEET (RULE 26) WO, 99/05096 _ PCT/US98/15386 1 H NMR (300 MHz, DMSO-d6) 8 2.13 (s, 1 H), 2.94 (m, 4H), 7.57 (dd, 1 H) 7.78 (dd> 1 H), 7.85 (s, 1 H), 8.01 (d, 1 H), 8.05 (d, 1 H), 8.43 (s, 1 H), 8.48 (m, 2H}, 9.06 (s, 2H), 9.40 (s, 2H);
MS (DCI/NH3) m/e 241 (M+H)+;
S Anal. caicd. for C 1 gH 16N20~ I .3TFA: C, 54.3 I ; H, 4.48; N, 7. I 9.
Found: C; 54.33; H, 4.35;
N, 7.27.
Example 47 6-(3-Methoxwhenyl)-2-naphthalenecarboximidamide mono~trifluoroacetate) salt io Example 47A
6-l3-Methoxvphen ly )-2-na~hthalenecarbonitriIe A solution of Example 28B (300 mg, 1 mmol), palladium (II) acetate (22 mg, 0.
I
mmol) and 1-I'-bis(diphenyphosphino)ferrocene (111 mg, 0.2 mmol} was stirred in DMF (3 15 mL) for 15 min, treated with Cs2C03 (813 mg, 2.5 mmol) and 3-methoxyphenylboronic acid (228 mg, 1.5 mmol), stirred for 20 min at 80 °C, cooled, treated with pH 7 buffer ( 10 mL} and extracted with diethyl ether. The ether extracts were dried (MgS04), concentrated and purified on silica gel with 10% ethyl acetate/hexane to provide 140 mg of the title compound as a white solid.
20 MS (DCI/NH3) m/e 277 (M+NH4)+.
Example 47B
6-(3-Methoxvnhenvl)-2-nanhthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 47A and the procedure of Example 1 B.
25 t H NMR (300 MHz, DMSO-d6) 8 3.88 (s> 3H), 7.03 (m, I H), 7.44 (m, 3H), 7.84 (dd, 1 H}, 11.05 (dd, 1 H), 8.19 (d, 1 H), 8.21 (d, I H), .4 t (s, 1 H), 8.5 i (s, 1 H), 9. I 1 (s, 2H), 9.45 (s, 2H);
MS (DCI/NH3) rn/e 277 (M+H)+;
Anal. calcd for C~gH~6N20~TFA~0.2H20: C, 61.03; H, 4.45; N, 7.I2. Found: C;
61.03; H, 30 4.11; N, 6.8b.
Example 48 N-f3-(methvl)phenvll-6-aminoiminomethvl-2-naphthalenecarboxamide mono(trifluoroacetate_) salt SUBSTITUTE SHEET (RULE 26) Examtile 48A
N-f3-(meth~phenyll-~~~ -c~ano-2-naphthalenecarboxamide The title compound was prepared from 3-methyl phenylis.ocyanate, Example 55C
and the procedure from Example 55C.
MS (DCUNH3) m/e 287 (M+H)+.
Exam le 4 B
N-f3-(methvi)phenvll-6-aminoiminometh 1-v 2-naphthalenecarboxamide mono(trifluoroacetate) The title compound was prepared from Example 48A and the procedure of Example 1 B.
1H NMR (300 MHz, DMSO-d6) 8 2.34 (s, 3H), 6.96 (d, 1H), 7.27 (t, IH), 7.62 (d, IH), 7.66 (s, 1 H), 7.91 (dd, 1 H), 8.15 (dd, I H), 8.29 (d, 1 H), 8.31 (d, 1 H), 8.54 (s, 1 H), 8.68 (s, iH), 9.15 (s, 2H), 9.49 (s, 2H), 10.46 (s, 1H);
MS (DCI/NH3) m/e 304 (M+H)+;
Anal. calcd for C19H17N30~TFA~0.12C-7Hg: C, 61.23; H, 4.46; N, 9.81. Found: C;
61.12;
H, 4.42; N, 9.43.
Example 49 6-(2-FormvlDhenoxv)-2-nanhthalenecarboximidamide monoltrifluoroacetate) salt Example 49A
6-f2-Formylphenoxv)-2-naphthalenecarbonitrile A solution of 2-hydroxybenzaldehyde (72 mg, 0.59 mmol), 6-bromo-1-cyanonaphthalene ( 150 mg, 0.65 mmol), and Cs2C03 (248 mg, 0.76 mmol) in DMF ( 10 mL) was heated at 90 °C for 2 days, treated with water and extracted with ethyl acetate. The combined organic extracts were dried (MgS04) and concentrated, and the crude product was purified by column chromatography with 10% ethyl acetate/hexane to provide 4f? mg of the title compound.
MS (DCI/NH3) m/e 291 (M+NHa)+.
Exam Ip a 49B
6-l2-FormvlDhenoxv)-2-naphthalenPcarboximidamide mono(trifluoroacetate) cult The title compound was prepared with Example 49A and the procedure of Example 1 B.

SUBSTITUTE SHEET (RULE 26) ~ H-NMR (300 MHz, DMSO-d6) 8 7.19 (d, 1 H), 7.44 (t, 1 H), 7.56 (s, 1H), 7.60 (d, 1 H), 7.79 (m, 2H), 7.94 (dd, 1 H), 8.01 (d, 1 H), 8.2 (d, 1 H), 8.S I (s, 1 H), 9.03 (s, 2H), 9.41 (s, 2H), 10.35 (s, 1H);
MS (DCI/NH3) m/e 291 (M+H)+.
S Anal. calcd. for ClgH~4N202~TFA~ 1.7H20: C, SS.16; H, 4.27; N, 6.43. Found:
C; SS.17;
H, 3.92; N, 5.94.
Exam 1e1~50, 6-(2-Formvlphenvl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt to Example SOA
6-(2-Formvlnhenyl)-2-navhthalenecarbonitrile The title compound was prepared from Example 28B, 2-formylphenylboronic acid and the procedure of Example 47A.
15 MS (DCI/NH~) m/e 27S (M+N3-14)+.
)Jxamnle SOB
6-f2-Formvlphenvl)-2-nanhthalenecarboximidamide mono(trifiuoroacetate) salt The tide compound was prepared from Example SOA and the procedure of Example 1B.
20 1H NMR (300 MHz, DMSO-d6) 8 7.71-7.64 (m, 2H), 7.79 (d, 1H), 7.81 (s, IH), 7.88 (dd, I H),7.9 (d, 1 H), 8.16 (d, I H), 8.23 (t, 2H), 8.56 (s, 1 H), 9.05 (s, 2H), 9.48 (s, 2H), 9.92 (s, 1 H);
MS (DCI/NH3) m/e 27S (M+H)+;
Anal. calcd for CIHH14N20~TFA: C, 61.86; H, 3.89; N, 7.21. Found: C; 61.98; H, 3.59; N, 25 6.88.
Example 51 6-f2-(Hvdroxymethvllohenvll-2-navhthalenecarboximidamide mono(trifluoroacetate) salt Example S 1 A
~-12-(Hvdroxvmethvl)1-2-naphthalenecarbonitrile Example SOA (98 mg, 0.38 mmol) and sodium borohydride ( 1 S mg, 0.80 mmol) were dissolved in methanol ( 10 mL) and stirred for O.S h. The solution was concentrated, and the _87_ SUBSTITUTE SHEET (RULE 26) residue was purified on silica gel with 30% ethyl acetate/hexane to provide 90 mg of the title compound.
MS (DCI/NH3) m/e 277 (M+NH4)+.
Example 1B
6-f2-(Hvdroxvmethvl)phenyll-2-naphthalenecarboximi~iamide mono(trifluoroacetatel salt The title compound was prepared from Example S 1 A and the procedure of Example 1 B.
1H NMR (300 MHz, DMSO-d6) 8 9.46 (s, 2H), 9.06 (s, 2H), 8.54 (s, 1H), 8.16 (t, 2H), 8.07 (s> IH), 7.85 (dd, IH), 7.74 (dd, IH), 7.63 (d, IH), 7.49-7.34 (m, 3H), 4.46 (s, 2H);
MS (DCI/NH3) m/e 277 (M+H)+;
Anal. calcd. for C1gH16N20~ 1.44TFA: C, 56.93; H, 3.99; N, 6.36. Found: C;
56.94; H, 3.88; N, 6.46.
S Exam~2 613-Oxo-1-bntenvll-2-nanhthalenecarboximidamide mono(trifluoroacetatel salt Example 52A
6-l3-Oxo-1-buten 1W-2-naphthalenecarbonitrile The title compound was prepared from methyl acrylate, Example 28B and the procedure of Example 41 A. MS (DCI/NH3) m/e 222 (M+H)+.
Exam Ie~52B
6-(3-Oxo-1-butenvl)-2-naohthalenecarboximidamid monoltrifluoroacetatel alt The title compound was prepared from Example 52A and the procedure of Example IB.
1 H NMR (300 MHz, DMSO-d6} 8 9.46 (s, ZH), 9.13 (s, 2H), 8.48 (s, 1 H), 8.38 (s, 1 H), 8.18 (d, I H), 8.15 (d> 1 H), 8.01 (dd, 1 H), 7.85 (dd, 1 H), 7.82 (d, 1 H), 7.03 (d, I H), 2.40 (s, 1H);
MS (DCI/NH3) m/e 239 (M+H)+.
Anal. calcd for Cj5H1q.N20~1.58TFA: C, 52.13; H, 3.75; N, 6.69. Found: C;
52.09; H, 3.63;
N, 6.64.
Examl la a 53 7-Methoxv-8-( 1 H-DVrazol-4 yl)-2-na~hthalenecarboximidamide bis(trifluoroacetate) salt _88_ SUBSTITUTE SHEET (RULE 26) Example 53A
7-hvdroxv-8-iodo-2-n~hthalenecarbonitriIe A mixture of 7-cyano-2-naphthol (22.3 g, 131.8 mmol), sodium carbonate (29.3 g, 277 mmol) and I2 (31.8 g, 125.2 mmol) in water (500 mL) and THF (80 mL) at 0 °C was stirred at room temperature for 3 h, acidified with 1 M HCl and extracted with ethyl acetate. The extracts were washed with saturated Na2S203 and brine, dried (Na2S04) and concentrated.
The product was recrystallized from ethyl acetate to yield 33 g of the title compound.
MS (DCI/NH3) m/e 313 (M+NH4)+.
Exam l S B
7-Methoxy-8-iodo-2-naphthalenecarbonitrile Example 53A (36.7 g, 124.2 mmol) in methanol (500 mL) and ethyl acetate (300 mL) was treated over 3 h with 2M trimethylsilyldiazomethane in hexane (260 mL), stirred for 24 h, t 5 concentrated and recrystallized from ethyl acetate to provide 36.4 g of the title compound.
MS {DCI/NH3) m/e 327 (M+NH4)+.
Example 53C
4-Iodo-I-ff2-(trimethylsilyl)ethox lv meth lv 1-1H-pyrazole A slurry of NaH ( 1.94 g, 48.5 mmol) in THF (40 mL) at 0 °C was treated with a solution of 4-iodopyrazole (8.97 g, 46.2 mmol) in THF (20 mL), stirred for I
h, treated with SEM chloride (9.00 mL, 50.8 mmol), stirred at room temperature for 1 h, poured into water and extracted with ethyl acetate. The extracts were washed with brine, dried (MgS04) and concentrated. The residue was chromatographed on silica gel with 10% ethyl acetate/hexanes to provide 14.4 g of the title compound.
MS (DCI/NH3) m/e 325 (M+H)+.
Exam le D
I -ff2-~Trimethv~i_Ivl)ethox l~methyll-IH-pyrazol4-yllboronic acid Example 53C (12.97 g, 40 mmol) in THF (250 mL) at -78 °C was treated with 2.5 M
butyliithium in hexanes ( 17.6 mL, 44 mmol), stirred at -78 °C for IO
min, treated with trimethyl borate ( 11.36 mL, 100 mmol), warmed to room temperature, treated with 3M HCl (400 mL) and extracted with ethyl acetate. The extracts were concentrated, and the residue was dissolved SUBSTITUTE SHEET (RULE 26) in 1 M NaOH (500 mL), extracted with diethyl ether, acidified with concentrated HCI and extracted with ethyl acetate. The extracts were washed with brine, dried (Na2S04), and concentrated. The residue was chromatographed on silica gel with ethyl acetate to provide 2.20 g of the title compound.
S MS (DCI/NH3) m/e I99 (M-B(OH)2)+.
Example 5 7-Methoxv-8-f I-1f2-(trimethvlsilvl)ethoxylmethyll-IH-pvrazol-4=yll-2-nanhthalenecarbonitrile Examples 53B (I.55 g, 5 mmol) and 53D (1.45 g, 6 mmol) were subjected to the procedure described in Example 47A to provide 1.64 g of the title compound.
MS (DCI/NH3) m/e 380 (M+H)+.
Examyle 53F
_7-Methoxv-8-l l H-pvrazol-4-yl)-2-naphthalenecarbonitrile A solution of Example 53E ( 1.84 g, 4.85 mmoI) in THF
( 10 mL) was treated with 1 M tetrabutylammonium fluoride in THF (24 mL), refluxed for 6 h and concentrated. The residue was chromatographed on silica gel with 1: I
ethyl acetate/hexanes to provide 0.88 g of the title compound.
MS (DCI/NH3) m/e 267 (M+NH4)+.
Exam 1e~53G
7-Methoxv-8-(1 H-nvrazol-4-vl)-2-naphthalenecarboximidamide bis(trifluoroacetate) salt The title compound was prepared from Example 53F and the procedure of Example I B.
~ H NMR (300 MHz, DMSO-d6) 8 3.89 (s, 3H), 7.60 (dd, 1 H), 7.71 (d, 1 H), 7.92 (s, 2H), 8.05 (d, I H), 8.12 (d, 1 H), 8.29 (s, 1 H), 9.33 (s, 2H), 9.34 (s, 2H);
MS (DCI/NH3) m/e 267 (M+H)+ ;
Anal. calcd. for C15H14N40~2.8TFA: C, 42.30; H, 2.90; N, 9.59. Found: C;
42.54; H, 3.1 l;
N, 9.03.
Example 54 7-Methoxv-8-iodo-2-nanhthaleneca_rhnxirrudamide mono(trifluoroacetate) salt The title compound was prepared from Example 53B and the procedure of Example 1 B.

SU9ST1TUTE SHEET (RULE 26) ~H NMR (300 MHz, DMSO-d6) 8 4.01 (s, 3H), 7.65 (m, 2H), 8.12 (d, IH), 8.15 (d, IH), 8.42 (s, 1 H), 9.14 (s, 2H), 9.52 (s, 2H);
MS (DCI/NH3) m/e 327 (M+H)+.
Anal. calcd for C12H12N20I~ I.2TFA: C, 37.28; H, 2.87; N, 6.04. Found: C;
37.35; H, 2.47;
N, 5.93.
Example 55 N-nhenvl-6-aminoiminomethvl-2-nanhthalenecarboxamide mono(methanesulfonate) salt Example 55A
2-T ifluoromethanesulfonvloxy-6-bromonaphthalene A solution of 6-bromo-2-naphthol (4.96 g, 22.25 mmol), N-phenyltrifluoromethanesulfonate (7.95 g, 22.25 mmol), and diisopropylethyIamine (7.75 mL, 44.5 mmol) in methylene chloride (25 mL) were stirred for 3 h at room temperature, t S poured into water and extracted with diethyl ether. The extracts were washed with brine, dried (MgS04), and concentrated. The residue was chromatographed on silica gel with 3% ethyl acetate/hexane to provide 7.89 g of the title compound.
MS (DCI/NH3j m/e 354 and 356 (M+H)+.
20 Example SSB
l-Bromo-2-naphthalenecarbonitriie Example SSA (7.89 g, 22.2 mmol) was combined with Zn(CN)2 ( I .33 g, I 1.33 mmol) and Pd(PPh3)4 (256 mg, 0.22 mmol) in DMF (50 mL), heated at 90° C for 3 h, cooled to room temperature, treated with saturated NaHC03 and extracted with diethyl ether.
25 The extracts were washed with brine, dried over (MgS04), and condensed. The residue was chromatographed on silica gel with 5% ethyl acetate/hexanes to provide 2.67 g of the title compound.
MS (DCI/NH3) m/e 231 and 233 (M+H)+.
3o Example 55C
N-phenyi-6-cyano-2-naphthalenecarboxamide A solution of Example 55B (224 mg, 0.965 mmol) in THF (3 mL) and hexanes ( 1 tnL) at -100° C was treated with 2.5 M butyllithium in hexanes (0.386 mL, 0.965 mmol), stirred at -100° C for 5 min, treated with phenyl isocyanate (0.115 mL, 1.06 mmol), warmed to room SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTlUS98/15386 temperature, treated with pH 7 buffer (0.5 mL) and concentrated. The residue was chromatographed on silica gel with 20% ethyl acetate/hexanes as eluent, to provide 54 mg of the title compound:
MS (DCI/NH3) m/e 273 (M+H}+.
Example 55D
N-nhenvl-6-aminoiminomethyl-2-naphthalenecarboxamide mono(methanesulfonate) salt A solution of Example 55C (52 mg, 0.191 mmol) in THF (2 mL) was treated with 1 M
lithium bis(trimethylsilyl)amide in THF (0.6 mL), stirred for 18 h, treated with 2M HCl (4 mL}, stirred for another 24 h, made basic with saturated Na2C03 and extracted with ethyl acetate. The extracts were washed with brine, dried (Na2S04) and concentrated.
The crude product was dissoved into a minimal amount of methanol (ca. l mL), treated with methanesulfonic acid (1 drop), diluted with diethyl ether (400 mL) and filtered to provide 15 mg of the title compound.
t5 t H NMR (300 MHz, DMSO-d6) 8 2.32 (s, 3H), 7.15 (dd, I H), 7.40 (dd, 2H), 7.83 (d, 2H), 7.90 (dd, I H), 8.17 (dd, 1 H), 8.25 (d, 1 H), 8.34 (d, 1 H), $.57 (s, 1 H), 8.70 (s, 1 H), 9.09 (br s, 2H), 9.51 (br s, 2H);
MS (DCI/NH3) m/e 290 (M+H)+.
Anal. calcd for CIgH~6N30~1.1 CH3S03H: C, 57.96; H, 4.95; N, 10.61. Found: C, 58.03;
H, 4.48; N, 10.36.
Examlhe 5656 4-ff6-Aminoiminomethyl-~-naphthalen I~ox~-methvlbenzeneacetamide mono(trifluoroacetate) salt Example 5 A
N-methyl-3-hydrox'~~lacetamide A solution of 3-hydroxyphenylacetic acid (1.00 g, 6.57 mmol) and oxalyl chloride (0.63 mL, 7.22 mmol) in methylene chloride (20 mL) was treated dropwise with pyridine (0.6 mL, 7.37 mmol), stirred for 90 min, poured into 40% aqueous methylamine (30 rrtL), stirred for IS min, concentrated, dissolved into 1 M HCl and extracted with ethyl acetate. The extracts were washed with brine, dried (MgS04) and concentrated. The residue was chromatographed on silica geI with ethyl acetate to provide 260 mg of the title compound.

SUBSTITUTE SHEET (RULE 26) MS (DCI/NH3) m/e 166 (M+H)+.
Example 56B
4-j(6-Cyano-2-naphthalenyi)oxxl-N-methylbenzeneacetamide A mixture of Example 56A (245 mg, 1.48 mmol), Example 55B (344 mg, 1.48 mmol) and Cs2C03 (530 mg, 1.63 mmol) in DMF (3 mL) was stirred for 72 h at 120 °C, cooled and chromatographed on silica gel with 1:1 ethyl acetate/hexanes to provide 54 mg of the title compound.
MS (DCI/NH3) m/e 317 (M+H)+.
Example 56C
4-f (6-Aminoiminomethvl-2-naphthalenyl)oxyl-N-methylbenzeneacetamide mono(trifluoroacetate) salt The title compound was prepared from Example 56B and the procedure of Example 55D.
~ H NMR (300 MHz, DMSO-d6) 8 2.33 (s, 3H), 2.58 (d, 3H), 3.42 (s, 2H), 7.05 (m, 2H),7.12 (d, 1 H), 7.40 (dd, 1 H), 7.45 (m, 2H), 7.79 (dd, 1 H), 7.98 (q, 1 H), 8.02 (d, 1 H), 8.15 (d, 1H), 8.49 (s, 1H), 8.99 (br s, 2H), 9.39 (br s, 2H);
MS (DCl/NH3) m/e 334 (M+H)+.
2o Anal. calcd for C~9H1~N302~ 1.5CH3S03H: C, 54.08; H, 5.28; N, 8.80. Found:
C, 53.80;
H, 5.37; N, 8.52.
Example 57 fi-12-(Methvlthio)nhenvll-2-naphthalenecarboximidamide mono(methanesulfonate) salt Example 57A
2-Cyanonaphthalene-6-boronic acid A solution of Example 55B (6.37 g, 27.45 mmol) in THF (220 mL) and hexanes (50 mL) at -100 °C was treated with 2.5 M butyllithium in hexanes ( 1 1.0 mL, 27.5 mmol), stirred at -100 3U °C for 10 min, treated with trimethyl borate (7.8 mL, 68.6 mmol), warmed to room temperature, treated with 3M HCl (400 mL) and extracted with ethyl acetate.
The extracts were concentrated and the residue was dissolved into 1 M NaOH (500 mL), extracted with diethyl ether, acidified with 12M HCl and extracted with ethyl acetate. The extracts were washed with SUBSTITUTE SHEET (RULE 26) brine, dried (Na2S04), and concentrated. The residue was dissolved into minimal methanol and ethyl acetate and triturated with hexanes to yield 2.74 g of the title compound.
MS (DCI/NH3) m/e 215 (M+NH4)+.
Exam ly a 57B
6-f 2-(Methylthio)phenvll-2-navzhthalene~arbonitrile A solution of 2-bromothioanisole (0.147 mL, 1.10 mmol), Pd(OAc)2 (24 mg, 0.11 mmol) and 1,1'-bis(diphenylphosphinoferrocene) (120 mg, 0.22 mmol) in DMF (5 mL) was stirred for 10 min, treated with Example 57A (260 mg, 1.32 mmol) and CszC03 ( 1.07 g, 3.3 mmol), heated at 85 °C for 6 h, cooled to room temperature and chromatographed on silica gel with 10% ethyl acetate/hexanes to provide 155 mg of the title compound.
MS (DCI/NH3) m/e 231 (M+NH4)+.
Exam le 57 is 6-f2-(Methylthio) hen Il-2-naohthalenecarboximidamide mono(methanesulfonate) salt The title compound was prepared from Example 57B and the procedure of Example SSD.
1 H NMR (300 MHz, DMSO-d6) 8 2.32 (s, 3H), 2.40 (s, 3H), 7.34 (m, 2H), 7.45 (m, 2H), 7.82 (dd, 2H), 7.95 (dd, 1 H), 8.06 (s, 1 H), 8.15 (d, 1 H), 8.20 (d, 1 H), 8.55 (s, 1 H), 9.03 (br s, 2H), 9.56 (br s, 2H);
MS (DCI/NH3) m/e 293 (M+H)+.
Anal. calcd for CIgHI~N2S~CH3S03H: C, 58.18; H, 5.18; N, 7.12. Found: C, 57.97; H, 5.31; N, 6.97.
Example 58 f~-f2-(2-Thiomethoxoxvethvl)phen,ylinaDhthalene-2-carboximidamide monolmethanesulfonate) Example ,S~iA
2-l2-Bromoethvllbromobenzene A solution of 2-bromophenethyl alcohol (5.05 g, 25.1 mmol) and pyridine (3.65 mL, 45.2 mmol) in acetonitrile (60 mL) was treated with Ph3PBr2 ( 13.8 g, 32.65 mmol), stirred at 0° C
for 2 h, diluted with hexanes and filtered through a plug of silica gel with 25% diethyl ether/hexanes to provide 6.0 g of the title compound.

SUBSTITUTE SHEET (RULE 26) MS (DCIJNH3) m/e 263 (M+H)+.
Example 58B
2-(2-Thiomethox-yethyl)bromobenzene A solution of Example 58A (990 mg, 3.75 mmol) and sodium thiomethoxide (290 mg, 4. I2 mmol) in DMF (5 mL) was heated at 90° C for 5 h, cooled and chromatographed on silica gel with 1 % ethyl acetate/hexanes to provide 646 mg of the title compound.
MS (DCI/NH3) m/e 231, 233 (M+H)+.
to Example 58C
6-(2-(2-Thiomethoxyethyl)phenyll-2-naphthalenecarbonitrile The title compound was prepared from Example 58B (300 mg, 1.30 mmol), Example 57A (260 mg, 1.32 mmol) and the procedure described in Example 57B.
MS (DCI/NH3) m/e 321 (M+NH4)+.
IS
Example 58D
6-12-(2-Thiomethoxoxvethvl)ohenvllnaphthaiene-2-carboximidamide mono(methanesulfonate~
st The title compound was prepared from Example 58C and the procedure from Example 2o SSD.
IH NMR (300 MHz, DMSO-d6) 8 I.78 (s, 3H), 2.31 (s, 3H), 2.55 (m, 2H), 2.85 (m, 2H), 7.30-7.48 (m, 4H), 7.66 (dd, 1 H), 7.85 (dd, I H), 8.04 (s, I H), 8.18 (d, 1 H), 8.20 (d, 1 H), 8.55 (s, 1H), 9.01 (br s, 2H), 9.43 (br s, 2H);
MS (DCI/NH3) m/e 321 (M+H)+.
25 Anal. calcd for CzpH2oN2S2~ I .35CH3S03H: C, 56.96; H, 5.69; N, 6.22.
Found: C, 57.08;
H, 5.49; N, 6. i 4.
Example 59 7-Methoxv-8-(3-furanvl)-2-naahthalenecarboximidamide mono(methanesulfonateZsalt Example 59A
7-Methoxv-8-l3-furanyl)-2-naphthalenecarbonitrile The title compound was prepared from Example 53B, furan-3-boronic acid (873 mg, 7.80 mmol) and the procedure of Example 57B.

SUBSTITUTE SHEET (RULE 26) MS (DCI/NH3) m/e 267 (M+NH4)+.
Example 59B
7-Methoxv-8-(3-furanvl)-2-naphthaienecarboximidamide mono(methanesulfonate) salt The title compound was prepared from Example 58C and the procedure from Example 55D.
1H NMR (300 MHz, DMSO-d6) 8 2.34 (s, 3H), 3.91 (s, 3H), 6.76 (s, 2H), 7.62 (dd, IH), 7.74 (d, 1 H), 7.87 (dd, I H), 7.96 (s, I H), 8.12 (d, I H), 8. I 5 (d, I H), 8.25 (s, 1 H), 8.96 (br s, 2H), 9.35 (br s, 2H);
n> MS (DCI/NH3) m/e 267 (M+H)+.
Anal. calcd for Ci~,H~4N202~CH3S03H: C, 55.77; H, 5.00; N, 7.63. Found: C, 55.73; H, 4.61; N, 7.4$.
Example 60 7-Methoxv-8-(2-benzofuranyl)naphthalene-2-carboximidamide monolmethanesuifonate) salt Example 60A
7-Methoxv-8-(2-benzofuranvi)-2-naphthalenecarbonitrile The title compound was prepared from Example 53B ( 166 mg, 0.5() mmol), benzofuran-2-2o boronic acid ( 1 13 mg, U.70 mmol) and the procedure of Example 57B.
MS (DCI/NH3) m/e 317 (M+NH4)+.
Example COB
7-Methoxv-8-(2-benzofuranyl)naphthalene-~-- c:arboximidamide mono(methanesulfonate) salt '_', The title compound was prepared from Example 60A (72 mg, ().240 mmol) and the procedure from Example 55D.
~H NMR (3(l0 MHz, DMSO-d~;) b 2.30 (s, 3H), 3.98 (s, 3H), 7.24 (s, 1H), 7.36 (m, 2H), 7.67 (m, 2H), 7.75 (m, I H), 7.84 (d, 1 H), 8.21 (d, 1 H), 8.30 (d, 1 H), 8.32 (s, 1 H), 8.88 (br s, 2H), 9.39 (br s, 2H);
3U MS (DCI/NH3) m/e 317 (M+H)+.
Anal. calcd for C2pH 1~N2O2~ 1.3CH3S03H: C, 57.98; H, 4.84; N, 6.35. Found: C, 57.79;
H, 4.78; N, 6.22.
Example 6I

SUBSTITUTE SHEET (RULE 26) (E)-H-f 2-( I ,3-Benzodioxol-5-vl)ethenyll-~-nar~hthalenecarboximidamide mono(methanesulfonate salt Exam le 1 A
(E)-S-f 2-( 1.3-Benzodioxol-5- 1)ethenvll-2-na~hthalenecarbonitrile Example 53B (75 mg, 0.243 mmol), PdCI2(dppf) (20 mg, 0.024 mmol), 3,4-methylenedioxystyrene (43 mg, 0.291 mmol) and diisopropylethylamine (0.170 mL, 0.97 mmol) in N-methylpymolidinone (2 mL) were stirred at 90° C for 18 h, cooled to room temperature and chromatographed on silica gel with 20°lo ethyl acetate/hexanes to provide 46 mg m of the title compound.
MS (DCI/NH3) mle 347 (M+NH4)+.
Example 61 B
(E)-H-f 2-( I ,3-Benzodioxol-5- llethenyl l-2-naphthalenecarboximidamide t5 mono(methanesulfonate) salt The title compound was prepared from Example 61 A (43 mg, 0.131 mmol) and Ehe procedure from Example 55D.
~H NMR (300 MHz, DMSO-d~,j 8 2.32 (s, 3H), 4.01 (s, 3H), 6.07 (s, 2H}, 6.96 (d, 2H), 7.10 (d, 2H), 7.32 (d, 2H), 7.45 (s, 1 H), 7.56 (d, 1 H), 7.66 (d, 2H), 7.72 (d, 1 H), 8.06 (s, 2c> 1 H), 8.03 (d, 1 H), 8.12 (d, 1 H), 8.66 (s, 1 H), 8.96 (br s, 2H), 9.44 (br s, 2H);
MS (DCI/NH3) m/e 347 (M+H)+.
Anal. calcd for C2t H I~N~03~ I .1 CH3S03I-l: C, 58.72; H, 4.99; N, 6.2().
Found: C, 58.77;
H, 5.07; N, 5.99.
--'s Example 62 ( ~ )-7-Methoxy-!~-(tetrahydro-3-furanyl -. )?-naphthalenec:arboximidamide mono(methanesulfonate) salt Example 62A
3O (~ }-7-methoxv-H-f3-hvdroxv-1-(hvdroxvmet~l)-1-hropenyll-2-naphthalenecarbonitrile A solution of Example 53B (3.09 g, 10 mmol), PdCI? (120 mg, 1 mmol), cis-2-butene-1,4-dioi ( 1.23 mL, I 5 mmol) and NaHCO~ ( I .() I g, 12 mmol) in N-methylpyrrolidinone ( 10 mLj was stirred at 130 °C for I h, cooled to room temperature and chromatographed on silica gel with SUBSTITUTE SHEET (RULE 2B) 30°lo ethyl acetate/hexanes to provide 2.19 g of the title compound as a mixture of diastereomers.
MS (DCI/NH3) m/e 269 (M+H)+.
Exam lp a f 2B
( ~ )-7-Methoxy-8-(tetrahvdro-3-furanyl)-2-naphthalenecarbonitrile Example 62A ( 140 mg, 0.52 mmol) in methylene chloride (3 mLj at 0 °C
was treated with triethylsilane (0.166 mL, 1.04 mmol) and BF3~OEt2 (0.096 mL, 0.78 mmol), stirred at room temperature for 4 h, concentrated and chromatographed on silica gel with 25010 ethyl lU acetate/hexanes to provide 100 mg of the title compound.
MS (DCI/NH3) m/e 271 (M+NH4)+.
Exam Ie~62C
(~ )-7-Methoxy-H-(tetrahydro-3-furanyl)-2-na~hthalenecarboximidamide t S mono(methanesulfonate) salt The title compound was prepared from Example 62B (96 m~, 0.379 mmol) and the procedure from Example 55D.
1 H NMR (300 MHz. DMSO-d~,) 8 2.20 (m, 1 H), 2.33 (m, 1 H), 2.39 (s, 3H), 3.99 (s, 3H), 3.90-4.03 (m, 3H ), 4.1 1 (m, 1 H), 4.42 (m, 1 H), 7.64 (d, 1 H), 7.68 (d, 1 H), 8.01 (d> 1 H), 2U 8.1 () (d, 1 H), 8.70 (s, 1 H), 9.01 (br s, 2H), 9.41 (br s, 2H), MS (DCI/NH3) m/e 271 (M+H)+.
Anal. calcd for C~~,H1gN202~1.2CH3S03H: C. 53.57; H, 5.96; N, 7.26. Found: C, 53.67;
H, 5.7X; N. 6.72.
Exam l f~-Il4-(2-Aminoethyl)phenyl lethvnvll-2-naphthalenecarboximidamide mono(trifluoroacetate) salt Example 63A
3U 6-(Trimeth~silyleth~n~l)-2-naphthalenecarbonitrile Example 28B and trimethylsilylacetylene were submitted to the conditions described in Example 42C to provide the title compound.
MS (DCI/NH3) m/e 267 (M+NH4)+.
_98_ SUBSTITUTE SHEET (RULE 26) Example 63B
6-Ethynvl-2-naphthalenecarbonitrile A mixture of Example 63A (t).4 g, 1.6 mmole) and K2C03 (U.4 g, 3.2 mmole) in methanol ( 16 mL) was stirred at room temperature for 18 h, concentrated, treated with water and extracted with methylene chloride. The organic layer was washed with U.5 NHCI and brine, dried (MgS04) and evaporated to provide the title compound.
MS (DCI/NH3) m/e 195 (M+NH4)+.
Examlale 63C
1u 4-Bromo-lN-tert-butoxycarbo ~l~ henethvlamine 4-Bromophenethylamine and di-t-butyldicarbonate were subjected to the conditions described in Synthesis, 48, 1986 to provide the title compound.
MS (DCI/NH3) m/e 319 (M+NH4}+.
S Example 63D
6-f 14-(2-N-tert-butoxycarbonvlaminoeth~lphe~l lethynyll-2-na~hthalenecarbonitrile The title compound was obtained with Examples 63B and C from the procedure described in Example 57B to provide the title compound.
MS (DCI/NH3) m/e 414 (M+NH4)+.
2() Exam l~E
6-I14-(2-Aminoethvl)z~henvllethvnvll-2-naphthalenecarboximidamide mono(trifluoroacetate~
salt The title compound was prepared with Example 63D and the procedure of Example 5B.
25 ~ H NMR (3U() MHz, DMSO-d~,) b 2.9U (t, 2H), 3.U9 (m, 2H) 7.36 (d, 2H), 7.60 (d, 2H), 7.76 (d, 2H), 7.76 (dd, IH), 7.85 (s, 2H), 7.87 (dd, 1H). 8.13 (d. 1H), 8.18 (d, 1H), 8.31 (s, I H), 8.5U (s, I H}, 9.18 (s, 2H), 9.45 (s, 2H);
MS (DCI/NH3) m/e 314 (M+H)+.
Anal. calcd for C21H19N3~2TFA~H20: C, 53.67; H, 4.14; N, 7.15. Found: C, 53.37; H, 3t~ 3.93; N, 7.17.
Exam lp a 64 7-Methoxv-8-12-pvrimidinvl(oxv)1-~-naphthaIenecarboximidamide mono(trifluoroacetatel SUBSTITUTE SHEET (RULE 26) Example 4A
7-Methoxv-8-f 2-Rvrimidinyl(oxy)1-2-naphthalenecarbonitrile Example 4A ( 125 mg, 0.627 mmol) and 2-chloropyrimidine ( 143 mg, 1.25 mmol) were subjected to the procedure described in Example 6A to provide 101 mg of the title compound.
MS (DCI/NH3) m/e 278 (M+H)+.
Example 64B
7-Methoxv-8-f2-twrimidinvltox )1-2-naphthalenecarboximidamide mono(trifluoroacetate) The title compound was prepared with Example 64A and the procedure of Example 1 B.
1 ~H NMR (300 MHz, DMSO-d~,) b 2.51 (s, 3H), 3.83 (s, 3H), 7.18 (t, 1H), 7.70 (dd, 1H), 7.80 (d, 1 H), 8.05 (d, 1 H), 8.19 {d, 1 H), 8.34 (s, 1 H), 8.62 (d, 2H), 9.07 (br s, 2H), 9.45 (br s, 2H);
MS (DCI/NH3) m/e 295 (M+H)+.
Anat. calcd for C?pH ~~N4O4~ 1.33TFA: C, 40.48; H, 2.60; N, 8.35. Found: C, 40.25; H, ~s 2.94; N, 8.92.
Exam 1» a 65 7-Methoxv-8-f2-thiazovi(oxv)lnaphthalene-2-carboximidamide mono(trifluoroacetate) salt ?« Example 65A
7-Methox~r-8-f2-thiazovl(oxy)1-~-naphthalenecarbonitrile A mixture of Example 4A (250 mg, 1.25 mmol), 2-bromothiazole (225 mL, 2.50 mmol) and CsF (2t)9 mg, 1.38 mmol) in DMSO (4 mL) was stirred at 120 °C for 4 days, cooled and chromatographed on silica gel with 30% ethyl acetate/hexanes to provide 162 mg of the title ?a compound.
MS (DC1/NH3) m/e 283 (M+H)+.
Example 65B
7-Methoxv-8-f2-thiazovl(oxvllna~hthalene-2-carboximidamide mono(trifluoroacetate) salt 3tl The title compound was prepared with Example 65A and the procedure of Example 1 B.
~H NMR (300 MHz, DMSO-d6) b 3.98 (s, 3H) 7.25 (m, 2H), 7.73 (dd, 1H), 7.86 (d, 1H), 8.12 (d, 1 H), 8.22 (d, 1 H), 8.35 9.09 (bs, 2H), (s, 1 H), 9.48 (bs, 2H).
MS (DCI/NH3) m/e 300 (M+H)+.
Anal. calcd for C~5H~3N30~S~TFA: C, 49.40; H, 3.41; N, 10.70. Found: C, 49.10;

SUBSTITUTE SHEET (RULE 26) H, 3.40; N, 10.69.
Exam I
7-Methoxv-8-(4-nitroDhenoxy)-~-naphlhalenecarboximidamide mono(,).rifluoroacetate) salt S
Example 66A
7-Methoxv-8-(4-vitro henoxv)-2-naohthalenecarbonitrile The title compound was prepared from Example 4A (125 mg, 0.627 mmol), 1,4-dinitrobenzene (i43 mg, 1.25 mmol) and the procedure described in Example 65A
to provide I~) 227 mg of the title compound.
MS (DCI/NH3) m/e 338 (M+NH4)+.
Examl la aIa a h6B
7-Methoxv-8-(4-nitroDhenoxv)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt 15 The title compound was prepared with Example 66A and the procedure of Example SSD.
I H NMR (300 MHz, DMSO-d~,) 8 9.43 (br s, 2H), 8.94 (br s, 2H), 8.25 (m, 4H), H.15 (d, I H), 7.88 (d, I H), 7.72 (dd, 1 H), 7.05 (d, 2H}, 3.91 (s, 3H), 2.30 (s, 3H};
MS (DCI/NH3) m/e 338 (M+H)+.
2u Anal. calcd for CIgH15N304~1.75CH3S03H: C, 46.93; H, 4.39; N, 8.31. Found:
C, 47.17;
H, 4.32; N, 8.I2.
Exam Ie~67 7-Methoxv-H-DentatluoroDhenox -?-naphthalenecarboximidamide mono(trit7uoroacetatel Salt ?S
Example 67A
7-Methoxv-8-pentafluorol henoxv-2-nanhthalenecarbonitrile Example 4A ( 100 mg, 0.50 mmol) and hexafluorobenzene ( I 15 mL, 1.00 mmol) were subjected to the procedure described in Example 65A to provide I50 mg of the title compound.
3o MS (DCI/NH3) m/e 383 (M+NH4)+.
Example fi7B
7-Methoxv-8-pentafIuoroDhenoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt SUBSTITUTE SHEET (RULE 26) The title compound was prepared with Example 67A and the procedure of Example 55D.
~ H NMR (300 MHz, DMSO-d6} 8 2.31 (s> 3H), 3.82 (s. 3H), 7.87 (dd, 1 H}, 7.88 (d, I H), 8.02 (d, I H), 8.20 (d> 1 H), 8.65 (s, 1 H), 9.04 (br s, 2H). 9.4? (br s, 2H);
S MS (DCI/NH3) m/e 383 (M+H)+.
Anal. calcd for CigH11N2F50~~1.2CH3S03H: C, 46.67; H, 3.19; N, 5.68. Found: C, 46.55;
H, 3.00; N, 5.58.
Exam I~e 68 7-Methoxv-R-fN-2-nhenvlaminoll-2-naphthalenecarboximidamide mono(trifluoroacetate~salt Example 68A
7-Methoxv-H-IN-2-phenvl(amina) 1-2-naphthalenecarbonitrile A solution of Example 25A (3()9 mg, l.()0 mmol), aniline (0.109 mL, 1.2 mmol), ~ 5 NaO~Bu ( 1 I 5 mg, I .2 mmol), Pd2(dba)3 ( 10 mg, 0.01 mmol) and dppf ( 17 mg, 0.03 mmol} in toluene (5 mL) was stirred for 3 h at I()0 °C, cooled and chromatographed on silica gel with 10% ethyl acetate/hexanes to provide 175 mg of the title compound.
MS (DCI/NH3) m/e 275 (M+H)+.
?O Example 6RB
7-Methoxv-H-(N-2-phenvlamino)-2-naphthalenecarbo~cimidamide mono(trifluoroacetate~ salt The title compound was prepared with Example 68A and the procedure of Example SSD.
~H NMR (3()() MHz, DMSO-d~,) ~ 3.95 (s, 3H), 5.92 (bs, 1H), 6.6i (d, 2H), 6.94 (t, 1H), ?5 7.1 fi (dd. 2H), 7.45 (dd. 1 H). 7.4H (d, 1 H), 7.7fi (d. 1 H), 7.)if; (d.
1 H), K.13 (d. 1 H), 9.()H
(bs, 2H), 9.31 (bs, 2H).
MS (DCI/NH3) m/e 292 (M+H)+.
Anal. Calcd for CigH~7N30~TFA: C, 59.26; H, 4.4H; N, 10.37. Found: C, 59.20;
H, 4.32; N, 10.1 S.
31) Example f 9 N-(6-Aminoiminometh 1-v 2-naphthalenyl)-N'-benzv)uren mono(trifluoroac.etate~
valt Example 69A

SUBSTtTUTE SHEET (RULE 26) WO 99105096 _ PCT/US98/15386 N-(6-Cvano-2-na_phthalenvl)-N'-benzylurea The title compound was prepared with Example 40A, benzylamine and the procedure from Example 40B.
MS (DCI/NH3) m/e 302 (M+H)+.
i Example 69B
N-(6-Aminoiminomethvl-2-nalahthalenyl)-N'-benzylurea mono(trifluoroacetate) salt The title compound was prepared with Example 69A and the procedure from Example 40D.
~ H NMR (300 MHz, DMSO-d6) 8 4.35 (d, 2H), 6.91 (t, I H}, 7.35-7.24 (m, SH), 7.59 (dd>
1> 1 H), 7.72 (dd, 1 H), 7.95 (d, 1 H), 7.96 (d, 1 H), 8.22 (d, 1 H), 8.35 (d, 1 H), 8.92 (br s, 2H), 9.13 (s, 1 H), 9.32 (br s, 2H).
MS (DCI/NH3) m/e 319 (M+H)+.
Anal. calcd for C~9H1RN40~TFA: C, 50.57; H, 4.24; N, 15.72. Found: C, 50.34;
H, 4.15;
N, 15.54.
IS
Example 70 N-(6-Aminoiminomethvl-2-naohthalenyl)-N'-methylurea mono(trifluoroacetate) salt Example 70A
2o N-(6-Cyano-2-naphthalenyl)-N'-meth, Iv urea The title compound was prepared with Example 40A (22I.2 mg, I .00 mmole) and methylamine (2.3 mL, 2.34 mmol) in THF ( 10 mL) according to the procedure from Example 40B.
MS (DCI/NH3) m/e 226 (M+H)+.
?5 Example 70B
N-(6-Aminoiminometh 1-v 2-naphthalenyl)-N'-methylurea mono(trifluoroacetate) salt The title compound was prepared with Example 70A and the procedure of Example 40D.
3U ~ H NMR (300 MHz, DMSO-df,} b 2.69 (d, 3H), 6.32 (q, 1 H), 7.60 (dd, 1 H), 7.73 (dd, 1 H), 7.93 (d, 1 H), 7.95 (d, 1 H, 8.19 (d, 1 H), 8.49 (d, I H), 9.09 (s, 1 H), 9. I 5 (br.
s, 4H);
MS (DCI/NH3) m/e 243 (M+H}+.

SUBSTITUTE SHEET (RULE 26) WO 99105096 PCTlUS98115386 Anal. calcd for C ~ ~H 14N40~TFA: C, 50.57; H, 4.24; N, 15.72. Found: C, 5Q.34; H, 4.15;
N, 15.54.
Example 71 N-(6-Aminoiminomethyl-2-naphthalenyl)-N'-isoprop~rlurea mono(trifluoroacetate) Salt Example 71 A
N-(6-Cyano-2-naphthalen 1 -N'-isopropvlurea The title compound was prepared with Example 40A, isopropylamine and the procedure it) from Example 40B.
MS (DCI/NH3) m/e 254 (M+H)+.
Example 71 B
N-(fi-Aminoiminomethvl-2-naphthalenyl)-N'-is~rop,~rlurea mono(trifluoroacetate) salt 1, The title compound was prepared with Example 71 A and the procedure of Example 5B.
~ H NMR (300 MHz, DMSO-d~) 8 1. I 3 (d, 6H), 3.76-3.114 (m, 1 H), 6.28 (d, I
H), 7.55 (dd, 1 H), 7.72 (dd, 1 H), 7.94 (d, 1 H), 7.95 (d, 1 H). 8. I 9 (d, i H), H.34 (d, 1 H), 8.85 (s, 1 I-I), 9.3 (br s, 2H), 9.0 (br s, 2H);
MS (DCI/NH3) m/e 271 (M+H)+.
2U Anal. calcd for C ~ 5H ~ gN40~TFA: C, 53.12; H, 4.98; N, 14.58. Found: C, 15.13; H, 4.84;
N, I 4.50.
Example 72 N~h-Aminoiminomethyl-2-naphthalenyl>-N'-phenyl-N'-methylurea mono(trifluoroacetate) salt ~5 Example 72A
N-(6-Cvano-2-naphthalenvl)-N'-phe~l-N'-methylurea The title compound was prepared with Example 40A, N-methyl-N-phenylamine and the procedure from Example 40B.
3c~ MS (DCI/NH3) m/e 302 (M+H)+.
Example 72B
N-(6-Aminoiminomethyl-2-naphthalenyl)-N'-phenyl-N'-methylurea mono(trifluoroacetate) salt The title compound was prepared with Example 72A and the procedure of Example 40D.

SUBSTITUTE SHEET (RULE 26) 1H NMR (300 MHz, DMSO-d~,} 8 3.33 (s, 3H), 7.25-7.47 (m, SH}, 7.7I-7.77 (m, 2H), 7.95 (two overlaping doublets, ZH), 8.16 (d, I H). 8.35 (d, 1 H), 8.64 (s, I H), 8.96 (br s, 2H), 9.34 {br s. 2H);
MS (DCI/NH3) m/e 319 {M+H)+.
S Anal. calcd for C2pH~7N40~TFA: C, 58.33; H, 4.43; N, 1 1.96. Found: C.
58.38; H, 4.69;
N, 1 I .82.
Example 73 6-Aminonaphthalene-2-carboximidamide mono(trifluoroacetate) salt Example 73A
6-Phenvlcarbamovl-2-naphthalenecarbonitrile The title compound was prepared from Example 40A, phenol and the procedure from Example 40B.
MS (DCI/NH~) m/e 289 (M+H)+.
Example 73B
6-Aminonaphthalene-2-carboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 73A and the procedure of Example 2c 4()D.
~H NMR (3()0 MHz, DMSO-d~,) 8 6.01 (br s, 2H), 6.86 (d, 1H), 7.06 (dd, 1H), 7.58-7.67 (m, 2H), 7.74 (d, 1H), 8.2I (d, IH), 8.74 (br s, 2H), 9.16 (br s, 2H);
MS (DCI/NH~) m/e 196 (M+H)+.
Anal. calc:d for C~~H1~~N3~TFA: C, 52.18; H, 4.04; N, 14.04. Found: C, 51.92:
H, 3.87; N, 25 13.80.
Example 74 N-(6-aminoiminomethyl-2-nanhthaIenyl)-N'-c cy lohexvlurea mono(trifluoroacetate) salt Example 74A
N-(6-Cvano-2-naphthalen i -N'-cyciohex lurea The title compound was preparedwith Example 40A, cyclohexylamine and the procedure from Example 40B.
MS (DCl/NH3) m/e 294 (M+H)+.

SU8ST1TUTE SHEET (RULE 26) WO 99105096 _ PCT/iJS98/15386 Exam 1R a 74B
N~(6-aminoiminomethvl-2-na hthalenyl)-N'-cvcloherylurea mono(trifluoroacetate) alt The title compound was prepared with Example 74A and the procedure of Example 40D.
~H NMR (300 MHz, DMSO-d~,) 8 1.14-1.39 (m, SH), 1.54-1.58 (m, 1H). 1.65-1.72 (m, 2H), 1.81-1.86 (m, 2H), 3.46-3.52 (m, 1 H), 6.36 (d, 1 H), 7.55 (dd, 1 H), 7.72 (dd, 1 H), 7.93 (d, 1 H), 7.95 (d, 1 H), 8.18 (d, 1H), 5.35 (d, i H), 8.87 (s, 1 H), 9.00 (br s, 2H), 9.28 (br s, 2H):
MS (DCI/NH3) m/e 31 1 (M+H)+.
m Anal. calcd for C19H21N40~TFA: C, 56.60; H, 5.46; N, 13.20. Found: C, 56.61;
H, 5.72;
N, 13.03.
Exam lie 75 N-(6-aminoiminomethvl-~-naphthalenyl)-N'-benzyloxyurea mono(trifluoroac;etate) salt i5 Example 75A
N-(6-cyano-2-naphthalenyll-N'-benzyloxyurea The title compound was prepared with Example 40A, O-benzylhydroxylamine and the procedure from Example 40B.
2a MS (DCI/NH3) m/e 318 (M+H)+.
Example 75B
N-(6-arninoiminomethvl-2-naphthalenyl)-N'-benzylo~urea mono(trifluoroacetate) salt The title compound was prepared with Example 75A and the procedure of Example 40D.
''s ~ H NMR (300 MHz, DMSO-d~) b 4.87 (s, 2H), 7.25-7.42 (m, 3H), 7.45-7.51 (m, 2H), 7.75 (dd, 1H), 7.75 (dd, 1H), 7.97 (d, 2Hj, 8.30 (d, 1H), 8.38 (d, 1H), 8.97 (br s, 2H), 9.21 (s, IH), 9.35 (br s, 2H), 9.77 (s, IH);
MS (DCI/NH3) m/e 335 (M+H)+.
Anal. calcd for C19H1~N402~TFA: C, 56.25; H, 4.27; N, 12.49. Found: C, 56.26;
H, 4.39;
3U N. 12.30.
Example 76 l , l-Dimethvlethvl I4-f f l6-aminoiminomethyl-2-naphthalenvl)aminolcarbonvllphenyllcarbamate mono(trifluoroacetate) Bait SUBSTITUTE SHEET (RULE 26~

Example 7C~A
fi-Amino-2-na~hthalenecarbonitriie Sulfuric acid (45mL) was treated with Example 40B (6.5 g), stirred for 30 min, warmed s to room temperature for 20 min, poured onto ice, diluted with water to approximately 500 mL, cooled to 0 °C and treated with 50°lo aq sodium hydroxide such that the temperature did not exceed 35 °C. The light solid which precipitated was filtered, washed with water to pH 7, dried under vacuum and purified on silica gel with 20% ethyl acetate/ hexanes to provide 3.3 g of the title compound. MS (DCI/NH3) m/e 1 fig (M+H)+.
IU
Example 7f B
1.1-Dimethvlethvl (4-1f(6-cyano-2-nap halenvllaminolcarbo~llphenyllcarbamate mono(trifluoroacetatel salt The title compound was prepared from Example 7f~A, 4-N-Boc-aminomethylbenzoic 1 S acrid, the procedure from Example 35B with methylene chloride in place of THF.
MS (DCI/NH3) m/e 417 (M+H)+.
Example 7f~C
I-Dimeth lyethy114-ff(fi-aminoiminomethyl-2-naohthalenvl)aminolcarbonvllphenvllcarbamate 2U mono(trifluoroacetate) salt The title compound was prepared with Example 76B and the procedure of Example 40D.
IH NMR (300 MHz, DMSO-d(,) 8 3.30 (s, 9H), 4.22 (d, 2H), 7.42 (d. ZH), 7.49 (t, 1H), 7.79 (dd, 1 H), 7.95-8.00 (m, 3H), 8.09 (d, 2H), 8.42 (s, 1 H), 8.63 {d, 1 H), 9. I 8 (br s, 4H), 10.58 (s, 1 H);
MS m/e 434 (M+H)+.
Anal. calcd for C~4H2~NSOyTFA: C, 59.5E~; H, 5.(l0; N, 10.29. Found: C, 58.55;
H, 4.ii5;
N, 10.41.
Examlhe 7777 3o N-lfi-(Aminoiminomethvl)-2-naphthalenvll-4-(aminomethvl)benzamide mono(trifluoroacetate) salt Exam In a 77A

SUBSTITUTE SHEET (RULE 26) N-f6-(Arninoiminomethvll-2-na hthalenvll-4-(aminornethvI)benzamide monoltrif7uoroacetate) A solution of Example 76B (35 mg, 0.07 mmole) in 1:1 TFA/methylene chloride was stirred at room temperature for 1 h then concentrated. The residue was dissolved in water ( I2 mL), filtered through a 0.45 filter and concentrated. The solid was suspended in diethyl ether and filtered to yield 27 mg of the title compound as a white solid.
~ H NMR (300 MHz, DMSO-d6) 8 4.17 (q, 2H), 7.65 (d, 2H}, 7.50 (dd, I H), 7.99 (dd, 1H), 5.06-8.12 (m, 4H), 8.30 (br s, 2H), 8.44 (d, 1H), 8.64 (d, 1H), 9. I 3 (br s, 2H), 9.40 (br s, 2H), 10.70 (s, 1 H);
lU MS (DCIJNH3) m/e 319 (M+H)+.
Anal. calcd for C~yH1gN40~2.25TFA~0.5H20: C, 48.34; H, 3.67; N, 9.59. Found:
C, 48.45;
H, 3.74: N, 9.45.
Example 78 1S Ethvl l6-(aminoiminomethvl)-2-naphthalenyljcarbamate monoltrifluoroacetate) salt Example 75A
Ethvl (6-cvano-2-nanhthalenyllcarbamate mono(trifluoroacetate) salt The title compound was prepared with Example 40A, ethanol and the procedure from 2o Example 40B.
MS (DCI/NH3) m/e 241 (M+H)+.
Exam Ie~78B
Ethvl ffi-(aminoiminomethvl)-2-naphthalenXllcarbamate mono(trifluoroacetate) salt ~s The title. compound was prepared with Example 75A and the procedure of Example 40D.
~H NMR (300 MHz, DMSO-d~,) 8 1.29 (t, 3H), 4.19 (q, 2H), 7.69 (dd, IH), 7.76 (dd, 1 H), 5.1 (d, 2H), 5.23 (d, 1 H), 8.35 (d, I H}, 9.()3 (br s, 2H), 9.33 (br s, 2H), 10.1 I (s, I H);
3O MS (DCIlNH3) rn/e 25R (M+H)+.
Anal. calcd for C~4H 15N30?~TFA: C, 51.76; H, 4.34; N, 1 1.32. Found: C, S
1.32; H, 4.15;
N, 10.93.
Example 79 SUBSTITUTE SHEET (RULE 26) 1,1-dimethvlethvl f4-fff6-aminoiminomethvll-~-nanhthale~l)aminolcarbonyllaminolph null carbamate mono(trifluoroacetate) salt Exam In a 79A
1,1-Dimethvl f4-fff(6-cyano-2-naphthalen~rl)aminolcarbonvllaminolphenyllcarbamate The title compound was prepared with Example 40B, 4-(N-tert-butoxycarbonylamino)-aminobenzene and the procedure from Example 40C.
MS (DCI/NH3) m/e 403 (M+H)+.
Example 79B
1,1-dimethvlethvl f4-fff6-aminoiminomethyl)- 2-naphthalenyl)aminolcarbonvllamino~hen,L
carbamate mono(trifluoroacetatel calr The title compound was prepared with Example 79A and the procedure of Example 40D.
l; ~ H NMR (30() MHz, DMSO-d~,) ~ 1.22 (s, 9H), 7.38 (s, 4H), 7.62 (dd, 1 H), 7.75 {dd, 1H), H.(>() (d, 2H), k.27 (d, 1H), H.3H (d, 1H}, H.77 (a, 1H), H.90 (br s, 2H), 9.16 (s, 1 H), 9.20 (s, 1 H), 9.33 (br s, 2H);
MS (DCI/NH3) m/e 420 (M+H)+.
Anal. calcd for C23H2SN503~2TFA: C, 56.28; H, 4.91; N, 13.13. Found: C, 56.1H;
H, 5.07;
2U N, 12.44.
Example SO
(E)-6-f2-(Phenvlthio)ethenvll-2-naphthalenecarboximidamide mono(trifluoroacetate) salt 'S Example R0A
(E)-f~-f 2-~Phenvlthio)ethenyll-~-naphthalenecarbonitrile The title compound waa prepared from Example SSB, phenylvinyl sulfide and the procedure of Example 57B.
MS (DCI/NH3j m/e 305 (M+NH4)+.
Example ROB
(E)-6-f2-(Phenvlthio)ethenvll-~-nalahthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 80A and the procedure of Example 1 B.

SUBSTITUTE SHEET (RULE 26) WO. 99/05096 PCT/US98115386 ~ H NMR (300 MHz, DMSO-d~,) 8 6.91 (d, 1 H), 7.52-7.33 (m, SH), 7.50 (d, 1 H), 7.75- 7.83 (m, 1H), 7.98-8.89 (m, 1H), 8.08-8.80 (m, 3H), 8.44 (m, IH), 9.03 (s, 2Hj, 9.40 (s, ZH);
MS {DCI/NH3) m/e 305 (M+H)+.
Anal. calcd for CIc~HI6N~S~I.1TFA: C, 59.55; H, 4.03; N, 6.57. Found: C, 59.53; H, 4.12;
S N, 6.60.
Example 81 (E)-6-f2-(2-Furanvllethenvll-2-naphthalenecarboximidamide mono(trifluoroacetate) salt »~ Example 81 A
2-Vinvlfuran A solution of methyl(triphenylphosphonium)bromide (26.78 g, 75 mmol) in toluene (80 mL) was treated with butyllithium in hexanes (27.5 mL, 68.75 mmol) then furfural (6 g, 62.5 mmol). stirred for 0.5 h and distilled at 69-72 °C to provide the title compound as a clear, 1 S e:oiorless liquid with some toluene contaminant.
MS (DCl/NH3j m/e 83 (M+H)+.
Example 81 B
(E)-6-12-(2-Furanyl)ethen I -2-naphthalenecarbonitrile 2o The title compound was prepared from Examples SSB and 81 A and the procedure of Example 57B.
MS (DCI/NH3) m/e 263 (M+NH4j+.
Example 81 C
25 (E)-6-I2-(2-Furanvl)ethenvll-2-naphthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example X 1 B and the procedure of Example 1 B.
~H NMR (30() MHz, DMSO-d~,} 8 6.61 (dd, lHj, 6.66 (d, IHj, 7.19 (d, 1H), 7.38 (d, 1H), 7.77 (d, 1 H). 7.80 (dd, 1 H), 8.14-7.97 (m, 3H), 8.44 (s, 1 H), 9.05 (s, 2H), 9.42 (s, ZH);
MS (DCI/NH3) m/e 263 (M+H)+.
3u Anal. calcd for C~7Ht3N~0~1.2TFA: C, 58.49; H, 3.85; N, 7.04. Found: C, 58.45; H, 3.78;
N, 7.36.
Example 82 (E)-6-12-(1H-Imidazol-1-vl)ethenvll-~-naphthalenecarboximidamide mono(trifTuoroacetate) salt SUBSTITUTE SHEET (RULE 26) Exam lp a R2A
(E)-6-f 2-( 1 H-Imidazol-1-yl )ethenvll-2-naa~hthalenecarbonitrile The title compound was prepared from Example SSB, 1-vinylimidazole and the procedure of Example 42C.
MS (DCI/NH3) m/e 263 (M+NH4)+.
Exam lp a 82B
E)-6-12-f IH-Imidazol-1-vl)ethenvll-2-naphthalenecarboximidamide mono(trifluoroacetatel salt ~U The title compound was prepared from Example 82B and the procedure of Example 40D.
1 H NMR (300 MHz, DMSO-d6) 8 9.44 (s, 2H), 9.14 (s, 2H), li.15 (d, I H), 8.17-~i.05 (m, 4H), 7.93 (d, 1 H), 7.84 (dd, 1 H), 7.59 (s, 1 H), 7.49 (d, 1 H);
MS (DCI/NH3j m/e 263 (M+H)+.
l, Anal. calcd for C~~,H13N.~~2.7TFA: C, 45.28; H, 2.97; N, 9.91. Found: C, 45.33; H, 3.52;
N. 9.79.
Examl 1~ a H3 (E)-4-f 2-(6-Aminoiminometh l-2-nanhthalenvl)ethe~llbenzenesulfonamide mono(trifluoroacetate) salt Examlole R3A
4-vinylsulfonamide A solution of thionyl chloride (7.5 mL) and 4-t-butylcatachol (45 mg, 0.3 nunoi) in ?~ DMF (9 mLj at () °C was treated with 4-vinylbenzene sulfonic acid sodium salt (3 g, 14.6 rnmol), stirred for 6 h, stored at -1 () °C for 3 days, poured into ice water and extracted with benzene. The organic layer was washed with water, dried (Na2S04), filtered and concentrated to provide 4-vilylsulfonyl chloride as a clear, colorless oil. A portion of the chloride (1 g, 4.95 mmol) was disslolved in THF ( 10 mL), cooled to 0 °C, treated dropwise with concentrated 3O ammonium hydroxide until gas evolution ceased and extracted with ethyl acetate. The combined extracts were dried (Na2S04), and concentrated to provide 707 mg of the title compound as a pale yellow solid.
MS (DCI/NH3j m/e 201(M+NH4)+.
SUBSTtTUTE SHEET (RULE 26) Example 83B
(E)-4-f2-(6-Cvano-2-naphthalenyl)ethenyllbenzenesulfonamide The title compound was prepared from Example SSB, Example 83A and the procedure of Example 57B.
MS (DCI/NH3) m/e 352 (M+NH4)+.
Example 83C
(E)-4-f 2-(6-Aminoiminomethvl-2-naphthalenyl)ethenyllbenzeneeulfonamide mono(trifiuoroacetateo calr W The title compound was prepared from Example 83B and the procedure of Example 40D.
t H NMR (300 MHz, DMSO-d~,) b 9.43 (s, 2H), 9.05 (s, 2H), 8.46 (s, 1 H), 8.21 (s, 1 H), 8.16-7.95 (m, 3H), 7.86 (s, 2H}, 7.84-7.67 {m, 2H), 7.62 (d, 1H), 7.4-7.36 (m, 2H);
MS (DCI/NH3) m/e 352 (M+Hj+.
t5 Anal. calcd for Ct9H~-7N~02S~1.SC2F302H: C, 50.84; H, 3.59; N, 8.11. Found:
C, 50.83;
H, 3.89; N. 7.88.
Exam lp a 84 E_)-4-12-l6-Aminoirninomethvl-2-naphthalenyl)ethenyllbenzoic acid monoltrifluoroacetate) salt Example 84A
(E)-4-f2-(6-Cyano-2-naphthalen 1 ethenyllbenzoic acid The title compound was prepared from Example SSB, 4-vinylbenzoic acid and the procedure of Example 57B.
~5 MS (DCI/NH3j m/e 300 (M+H)+.
Example 84B
E)-4-f2-(6-Aminoiminomethyl-2-naphthalenvl)ethenyllbenzoic acid mono(trifluoroac;etate) salt The title compound was prepared with Example 84A and the procedure of Example 3u 40D.
iH NMR (300 MHz, DMSO-d~,) ~ 7.62 - 7.58 (m, 2H), 7.90 (d, 2H), 7.98 (d, 1H), 8.12 -8.04 (m, 3H), 8.20 (s, 1 H), 8.56 (s, 1 H), 9.07 (bs, 2H), 9.35 (bs, 2H).
MS (DCI/NH3) m/e 317 (M+H)+.
Anal. calcd for C2pHl~,N~02~TFA: C, 61.40; H, 3.98; N, 6.51. Found: C, 61.10;

SUBSTITUTE SHEET (RULE 26) WO 99/05096 _ PCTIUS98115386 H, 3.63; N, 6.45.
Example 85 4-f7-(Aminoiminomethvl)-2-methoxv-1-na htp halenylldihvdro-2(3H)-furanone monoftrifluoroacetate) salt Exam lp a 85A
4-(7-Cvano-2-methoxy-1-nanhthalenvl)dihydro-2(3H)-furanone Example 62A (269 mg, 1.00 mmol) and pyridinium chlorochromate (360 mg, 1.67 mmol) in lu methylene chloride ( 15 mL) were stirred at room temperature for 24 h, filtered through Celite~
and concentrated. The residue was chromatographed on silica gel with 20% ethyl acetate/
hexanes to provide 170 mg of the title compound.
MS (DCI/NH3) m/e 285 (M+NH4)+.
Exam to a H5B
4-l7-lAminoiminomethvl)-2-methoxy-1-n_aphthalenvl ldihydro-2(3H)-furanone mono(trifluoroacetate) salt The title compound was prepared from Example 85A and the procedure of Example 40D.
2v} ~ H NMR (300 MHz, DMSO-d6) S 2.96-2.75 (m, 2H), 3.96 (s, 3H), 4.33 (m, 1 H), 4.66 (t, 1 H), 8.85 (m, 1 H), 7.68 (dd, 1 H), 7.73 (d, I H), 8.08 (d, 1 H), 8.12 (d, 1 H), 8.67 (s, 1 H), 9.14 (s, 2H), 9.43 (s, 2H);
MS (DCI/NH3) m/e 285 f M+H)+.
Anal. calcd for CI~,H1~N~03~1.1TFA: C, 53.72; H, 4.24; N, 6.91. Found: C, 53.75; H, 4.26;
'?5 N, 6.94.
Example 86 7-Methoxv-8-(I-acetyl-1 H-nvrazolvl)-2-naphthalenecarboximidamide mono(trifluoroacetate) io Example 86A
7-Methoxv-8-( 1-acetyl-1 H-Ryrazolyll-2-na~hthalenecarbonitrile A solution of Example 53F (90 mg, 0.361 mmol) in THF (2 mL) was treated with a 0.5 M
solution of potassium bis(trimethylsilyl)amide in toluene (0.866 mL, 0.433 mmol), stirred for 5 SUBSTITUTE SHEET (RULE 2fi) min, treated with acetyl chloride (38 mL, 0.542 mmol), stirred for 10 min and concentrated.
The crude product was chromatographed on silica gel with 2590 ethyl acetate/hexanes to yield 67 mg of the title compound.
MS MS (DCI/NH3) m/e 309 (M+NH4)+.
Example 86B
7-Methoxv-8-(1-acetyl-1H-ovrazoivl)-2-naphthalenecarboximidamide mono(trifluoroacetate) The title compound was prepared with Example 86A and the procedure of Example 1c~ 40D.
~H NMR (300 MHz, DMSO-d~) 8 3.89 (s, 3H), 7.59 (d, 1H), 7.92 (s, 2H), X.06 (d, I H), 8.12 (d, I H), 8.28 (s, 1 H), 8.94 (s, 2H), 9.34 (s, 2H);
MS (DCI/NH3) m/e 309 (M+H)+.
Anal. calcd far C«H~~,N40y1.9TFA: C, 47.59; H. 3.44; N, 10.67. Found: C, 54.03; H, i s 4.06; N, 13.26.
Example S7 7-Methoxv-8-f 1-(methvlsulfonvl)-1 H-4-pyrazolyl -2-naphthalenecarborimidamide mono(trifluoroacetate) salt ?u Example 87A
7-Methoxv-8-f I-(methvlsulfonyl)-1 H-4-n~rrazolyll-2-naphthalenecarbonitrile The title compound was prepared from Example 53F (19() mg, 0.762 mmol), methanesulfonyl chloride (().(lHH mL, 1.14 mmol) and the procedure of Example 86A to ?s provide 122 mg of the title compound.
MS (DCI/NH~) m/e 345 (M+NH4)+.
Example 87B
7-Methoxv-8-fl-(methvlsulfonvl)-1H-4-p azol Ivl-2-n~,phthalenecarboximidamide mono(trifluoroacetate) salt The title compound was prepared from Example 87A and the procedure of Example 4(1D.

SUBSTITUTE SHEET (RULE 26) 1H NMR (300 MHz, DMSO-d6) 8 2.75 (s, 3H), 3.98 (s, 3H) 7.64 (dd, IH), 7.78 (d, 1H), 8.15 (s, I H), 8.18 (s, I H), 8.21 (s, 1 H), 8.24 (s, 1 H), 8.62 (s, 1 H), 8.97 {s, 2H), 9.40 (s, 2H);
MS (DCI/NH3) m/e 345 (M+H)+.
s Anal. calcd for C16H16N403S~ 1.4TFA: C, 44.75; H, 3.47; N, 1 I.09. Found: C, 44.59; H, 3.86; N, 11.38.
Example 88 (E)-4-f2-(6-Aminoininomethyl-2-naDhthalenyl)ethenvllbenzamide mono(trifluoroacetate) salt IU
Example 88A
(E)-4-f 2-(6-Cyano-2-naphthalenvl )ethenyllbenzamide Example 85A (16() mg, 0.54 mmol) in thionyl chloride (4 ml) was refluxed for 0.5 h, cooled to (1 °C, treated with concentrated aqueous ammonia until gas evolution ceased, diluted 15 with ethyl acetate, heated to dissolve residual solids, washed with water, dried (MgS04) and concentrated to provide 1 (>(1 mg of the title compound as an orange solid.
MS (DCI/NH3) rn/e 316 (M+NH4)+.
Example 88B
2c) (E)-4-f2-(6-Aminoininomethyl-2-naphthalenyl)ethenvllbenzamide mono(trifluoroacetatel salt The title compound was prepared with Example 88A and the procedure of Example 1 B.
~ H NMR (300 MHz, DMSO-d6) S 7.34 (br, 1 H), 7.51 (d, 1 H), 7.56 (d, 2H), 7.73 (d, 2H), 7.82 (m, 2H), 7.9(1 {d, 2H), 7.96 (br, 1 H), 8.09 (q, 3H ), 8.17 (s, 1 Hj, 8.43 (s, 1 H), 9.01 (s, 2H), 9.4(I (,, 2H):
25 MS (DCI/NH3 ) m/e 316 (M+H)+.
Anal. calcd for C2trH pN30~ 1.1 TFA: C, 60.()9; H, 4.1 1; N, 9.44. Found: C, 60.22; H, 4.13;
N, 8.79.
Exa die 89 6-f2-(4-Aminonhenv!)ethoxvl-2-naphthalenecarboximidamide mono(trifluoroacetate) salt Example 89A
6-f2-(4-Aminovhenyl)ethoxy -2-n~hthalenecarbonitrile -1 t5-SUBSTITUTE SHEET (RULE 26) WO 99/05096 _ PCT/US98115386 A solution of Example 4A, (300 mg), Cs2C03 ( 1.2 g ), 4-aminophenethylbromide {470 mg) and tetrabutylammonium iodide ( 10 mg j in DMF (5 ml) was stirred for 18 h at room temperature, diluted with water and extracted with ethyl acetate. The organic extract was washed with saturated aq NaHC03 and brine, dried (Na2S04) and concentrated to provide 200 s mg of the title compound as a dark brown oil.
MS (DCI/NH3) m/e 306 (M+NI-~)+.
Example 89B
6-I2-(4-Aminophenvl)ethoxvl-2-naphthalenecarboximidamide mono(trifluoroacetate) salt 1n The title compund was prepared with Example 89A according to the procedure of Example SB.
1 H NMR (300 MHz, DMSO-d~,) 8 3.15 (t, 2H), 3.6 (bs, 3H), 4.35 (t, 2H), 6.93 (d, 2H), 7.24 (d. 2H) 7.38 (dd, 1 H). 7.55 (d. 1 H), 7.78 (dd, 1 H), 7.98 (dd, 1 H), 8.21 (d, I H), 8.4 (d, 1H), 9.21 (bs, 2H1, 9.39 (bs, 2H);
I i M S m/e 30 fi ( M+H')+.
Anal. calcd for C~9H19N30~2TFA: C, 51.79; H, 3.97; N, 7.88; Found: C, 50.99;
H, 4.6H; N, 7.59.
Exam I
21~ Methvl f 3-methoxv-6-(aminoiminomethyl)-4-na hthalen I lcarbamate mono(trifluoroacetate) salt Example 90A
7-Methoxv-2-trifluoromethanesulfonyloxv naphthalene A solution of 7-methoxy-2-naphthol (3.24 g, 18 mmole) in DMF {20 mL) and methylene chloride (2() mL> was treated with N-phenyl trifluoromethanesulfonimide ((~.f~ g, 18 mmole> and triethylacnine (5.2 mL, 37 mmole), stirred 20 h at room temperature, diluted with CH2Cl2 ( 10() mL) , washed sequentially with distilled water, 20 % KOH and brine, dried (MgS04) and concentrated to provide the title compound as a clear oil.
MS (DCI/NH3): m/e 272 (M + NH4)+.
Example 90B
7-Methox -2-naphthalenecarbonitrile_ Example 90A ( 12 mmole), zinc cyanide ( 12 mmole}, Pd(OAc)2 (0.3 mmole) and triphenylphosphine (1.2 mmole} in DMF (40 mL) was heated for 6 h at 85 °C, diluted with SUBSTITUTE SHEET (RULE 26) ethyl acetate (200 mL), washed with saturated NaHC03, brine, dried (MgS04) and concentrated to a dark oily residue. Purification of the residue on silica gel with 1:1 hexane:
methylene chloride then CH2C12 provided 1.S g of the title compound as a white solid.
MS (DCI/NH3) m/e 201 (M + NH4)+.
Example 90C
7 -Methox~8-nirro-2-naphthalenecarbonitri~
Example 90B (3 g, 16.4 mmole) in acetic anhydride (30 mL,) at 0 °C was treated with fuming HN03 (1.2 mL), and the resulting thick slurry was diluted with water (20 mL), stirred IU 20 min then filtered and dried in vacuo to provide 3.69 g of the title compound as a yellow solid.
MS (DCI/NH3) m/e 246 (M+NH4)+.
Example 90D
7-Methoxy-H-amino-~-n~phthonitrile Example 90 C (3.69 g, 16.1 mmole) and 1 O~lc Pd/C (0.4 g) in ethyl acetate ( 100 mL) was stirred under a hydrogen atmosphere for 2 h at room temperature, filtered and concentrated to provide 3 g of the title compound as a yellow solid.
MS (DCI/NH3) rn/e 217 (M+NH4)+.

Example 90E
Methvl f3-methox~~ano-4-na hthalenyllcarbamate Example 90D (R 1 mg, 0.41 mmol) in dioxane (7 mL) and 10% NaOH ( 15 mL) was treated with methyl chloroformate (1 l2 mg. 0.9H mmoij, stirred for 2 h, diluted with ethyl 5 acetate, washed with water, dried (MgS04) and concentrated to provide 105 me of the title compound. MS (DCI/NH~) m/e 274 (M+NH3)+.
Example 90F
Methvl f3-methoxv-6-(aminoiminomethyl -1 4-n~phthalenyllcarhamate mono(trifluoroacetate) salt 3u The title compound was prepared from Example 9()E according to the procedure of Example 40D. tH-NMR (300 MHz, DMSO-d~,) 8 9.48 (s, 2H), X.99 (s, 2H), 8.93 (br, 1H), H.34 (s, 1 H), H.12 (d, 1 H), 8.04 (d, I H), 7.72 (d, 1 H), 7.65 (dd, 1 H), 3.95 (s, 3H);
MS (DCI/NH~) m/e 274 (M+H)+;

SUBSTITUTE SHEET (RULE 26) Anal. calcd for CIqHiSN3O3~l.HTFA: C. 44.07; H, 3.53; N, 8.74. Found: C, 44.14; H, 3.20;
N, 8.53.
Example 91 7-Methoxv-8-(2-nvrimidinvl(amino)1-2-naphthalenecarboximidamide bis(trifluoroacetate) salt Example 91 A
7-Methoxv-8-(2-nvrimidinyllamino)1-2-n~hthalenecarbonit~ile A solution of Exampie 90D (23U mg, 1.2 mmole), 2-chloropyrimidine (280 mg, 2 lu mmole), sodium-tent-butoxide ( 12() mg, I .2 mmole), Pd(dba)3~CHCl3 and dppf in toluene (5 mL) was heated in a sealed tube for 18 h at 100 °C, diluted with ethyl acetate ( 100 mL), washed with brine, dried (MgS04j and concentrated to provide 100 mg of a brown oil.
MS (DCI/NH3) m/e 294 (M+NH4)+.
15 Example 91 B
7-Methoxv-8-(2-nvrimidinyl(amino)1-~-naphthalenecarboximidamide bis(tritluoroacetate) salt The title compound was prepared in a manner analogous to that of Example 40D.
IH-NMR (30() MHz, DMSO-d6) b 9.43 (s, 2H), 9.1 1 (s, ZH), 8.46 (s, 1H), 8.16 (br, 3H), 8.15 ld, 1 H), lS.04 (d, 1 H), 7.82 (dd, 1 H), 7.75 (d, 1 H), 7.54 (s, i H) 7.50 (d, 1 H), 4.08 (d, 2H);
?u MS (DCI/NH3) m/e 294 (M+H)+.
Anal. calcd for C1~,HISN50~3.8TFA: C, 39.01; H, 2.61; N,9.64; Found: C, 39.01;
H, 3.06;
N, 9.63.
Example 92 6-(aminoiminomethvl )-N-(4-(hydrorymet~l)phenyl l-~-naphthaienecarboxamide '-S mono(trifluoroacetate)(salt) Example 92A
4-amino-benzyloxv-rert-butyldimethylsilyl ether A solution of 4-aminobenzyl alcohol (1 g, 8.1 mmolj in DMF (20 mL) was treated with 3u imidazole (0.54 g, X. I mmol) and tent-butyl dimethylsilyl chloride ( 1.22 g, 8.12 mmol), stirred overnight at room temperature, diluted with ethyl acetate ( 100 mL), washed with 1 N H3P04, saturated NaHCO~ and 10~c NaCI, dried (Na2S04) and concentrated to an oil which was purified on silica gel with 3: 1 hexanes: ethyl acetate to provide 0.5 g of a clear oil.
MS m/z 238 (M+H)+.

SUBSTITUTE SHEET (RULE 26) Example 92B
Example 92A (0.3. 1.1 mmol) and 6-carboxy-2-naphthonitrile, Example 8E (0.2 g, mmol) were processed as described in Example 95C to provide 100 mg of the desired compound.
MS m/z 434 (M+NH4)+.
Example ~2C
A solution of Example 92B in 1 M tetrabutyl ammonium fluoride THF solution (2 mL) m was stirred for I hour at room temperature, quenched with 10~/o NH4Cl solution (50 mL) and diluted with ethyl acetate ( 100 mL). The layers were separated, and the organic layer was washed with 10% NaCI, dried (MgS04) and concentrated to provide a light brown oil which was triturated with methylene chloride and filtered to provide 0.1 g of the desired compound as a white solid.
li MS m/z 320 (M+NH4)+.
Example 92D
6-laminoiminomethvl)-N-f4-(hydroxymeth~phenyl -~-na~hthalenecarboramide mono(trifluoroacetate)(Salt~
20 Example 92C (0.1 g, 0.33 mmol) was processed and purified according to the procedure in Example 95D to provide 15 mg of the desired compound.
MS m/z 320 (M+H)+;
~H NMR 30() MHz, (DMSO-d~,): 8 1().45 (s, 1H), 9.45 (bs. 4H), 8.75 (s, 1H), 8.59 (s, 1H), H.32 (d, E H), H.22 (d, 1 H), 8.1 H (dd, 1 H ), 7.92 (dd, 1 H), 7.85 (d, 2H), 7.45 (d, 2H), 4.2() S (~.2H);
Anal. calc'd for C~yH~7N30?~TFA: C, 5k.20; H, 4.19; N, 9.7(1. Found: C. 57.H0;
H, 3.91;
N, 9.35.
Example 93 3n 6~4-aminoDhenvl)-2-naphthalenecarboximidamide bis(trifluoroacetate) salt Ex' mple 93A
6-cyano-2-naphthalene boronic acid (0.3 g, 1.64 mmol), 4-iodoaniline (0.36 g, 1.64 mmol), Palladium[1, I'-Bis (diphenylphosphino)-ferrocene~ dichloride (0.13 g, 0.164 mmol) SUBSTITUTE SHEET (RULE 26) and CsF (0.75 g, 4.92 mmol) are mixed together in DMF ($ mL) heated 20 hours.
at HO °C.
The mixture is diluted with ethyl acetate ( 100 tnL) washed with 1 N H3P04, saturated NaHCO~, 10% NaCI, dried over anhydrous sodium sulfate. The drying agent filtered, solvent removed under vacuum leaving a brown solid. The solid is purified on silica gel eluting with 3:
1 hexanes: ethyl acetate. The fractions corresponding to the desired compound are concentrated under vacuum leaving a yellow solid. 0.2 g, 75%.
MS (M+NH4+): 262.
Exam~he 93B
U) 6-(4-aminophenvl)-2-naphthalenec~rboxitnidamide bis(trifluoroacetateo salt The desired compound is obtained from the material prepared in Example 93A
(0.1 g, 0.41 mmol) using the procedure described in Example 94D Yield: 35 mg, 53%
MS (M+H)+262;
is t1-I NMR 30t) MHz, (DMSO-d~~): 89.45 (bs, 2Hj, 9.35 (bs, 2H), 8.45 (d, 1H), 8.22 (s, IHj, 8.15 (d, 1 H j, 8.1 t) (d, I H), 7.99 (dd, I H), 7.79 (dd, I H), 7.65 (d, 2H), 6.95 (d, 2H), 4.80 (bs, 3H);
Anal. c:alc'd: C?tHI~N~O~,F~: C, 51.54, H, 3.50, N, 8.59, Found: C, 51.95, H, 3.84.
'« Example 95 methyl 2-I4-lllfi-(aminoiminomethyl)-2-na_phthalenvllcarbonvllaminolphenoxylacetate mono(trifluoroacetate) salt Example 95A
25 4-Acetamidophenol ( 5 ~, 33 mmol) is dissolved in THF ( I (?() mL) treated with Cesium c:urbonate (10.25 g, 33 mmol) and Methyl bromoacetate (3.4 mL, 36 mmol) and stirred 24 hours at room temperature. The reaction mixture is diluted with water ( 100 tnL) and concentrated under vacuum. The residue is dissolved in ethyl acetate ( 100 mL) washed with I
N H3P04 (20 mL), saturated NaHCO~ (20 mL), 10% NaCI (20 mL) and dried over anhydrous 3U Na2S04. The drying agent is filtered and the solvent removed under vacuum leaving the desired compound as a white solid, 6.8 g, (92%).
MS (M+NH4+): 241.
Example 95B

SUBSTITUTE SHEET (RULE 26) The material obtained in Example 95A is treated with 2 N HCl (75 mL) and refluxed for 3 hours. The clear mixture is cooled to room temperature then concentrated under vacuum to an off white solid as the desired compound. 6 g, 92~1c.
MS (M+NH4+): 195.
S
Exam lp a 95C
6-carboxy-2-naphthonitrile (0.1 g, .51 mmol) is dissolved in DMF (5 mL) cooled in an ice bath to 5 °C. To the homogeneous mixture is added Diisopropylethylamine (0.18 mL, 1.05 mmol) and O- (7-Azabenzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate n> (HATU). The resultant slurry is stirred at 5 °C 45 minutes. To this slurry is added the material obtained in Example 95B (0. I 2 g, .56 mmol) and the mixture is stirred at room temperature overnight. The next day, the reaction mixture is diluted with ethyl acetate ( 100 mL) washed with 1 N H~P04 (20 mL), saturated NaHC03 (2() mL), 10°lo NaCI, dried over anhydrous Na2S04 filtered and solvent removed under vacuum yielding the desired compound as a brown 15 solid. ().2H g, 65%.
MS (M+NH4)+: 375.
Example 95D
methyl 2-14-if ff-laminoiminomethvl)-~-naphthalenyllcarbonvllamino~henoxylacetate ?~~ mono(trifluoroacetate) salt The material obtained in Example 95C (0.25 g, .75 mmol) is dissolved in methanol saturated with HCl (g) (30 mLj stirred 15 hours at room temperature. The solvent removed under vacuum and the resultant yellow solid is treated with 2 M NH3/methanol (20 mLj. This solution is refluxed 6 hours, cooled, solvent removed under vacuum and the resulting brown s solid is purified by reverse phase HPLC. The desired compound is obtained from lyophilization. 19.3 mg, 2()c'/c.
MS (M+H)+: 375 ~ HNMR 300 MHz, (DMSO-d~,): 8 10.45 (s, 1 H), 9.45 (bs, 4H), 5.65 (d, 1 H), 8.59 (s, 1 H), 5.15 (d, 1 H), 5.1 U (d, 1 H), 5.05 (d, I H), 7.92 (d, 1 H), 7.75 (d, 2H), 6.95 (d, 2H), 4.50 (s, 3U 2H), 3.75 (s, 3H), Anat. calc'd: C23H~1N30~,F3: C, 56.10, H, 4.3, N, 5.53, Found: C, 55.80, H, 3.93, N, 5.33.
Example 96 (E)-E-12-1(3-hvdroxvmethvllDhen Il~ethe_null-~-naphthalenecarboximidamide SUBSTITUTE SHEET (RULE 26) WO 99(05096 PCT/US98I15386 mono(trifluoroacetatel(salt) Example 96A
The above was prepared from 3-iodobenzyl alcohol using the procedure in Example s 41 A.
MS (DCI/NH3) m/z (M+NH3)+ 303.
Example 96B
(E)-6-(2-1 (3-hvdroxvmethvl)phenyl(ethenyll-2-naphthalenecarboximidamide monoltrifluoroacetate)(~lt~
The above was prepared from Example 96A using method from Example 40D.
MS (DCI/NH3) rn/z (M+H)+ 303;
~ H-NMR (300 MHz, DMSO-d~) b 9.18 (br, 4H), 8.45 (s, 1 H), 8.17 (s, I H), 8.13-8.04 (m, 3H). 7. H 1 (dd, 1 H ), 7.64 (s. 1 H), 7.57 (d, 2H), 7.51 (d, I H) 7.39 (t, I
H), 7.28 (d, I H), I s 5.27 (t, 1 H ), 4.55 (d, 2H);
Anal. calc'd for C22H19N~03F3 3/10 TFA: C, 60.64; H, 4.35; N, 6.28. Found: C, 60.53; H, 4.87; N, 6.57.
Example 97 20 6-(2-phenyl-1-cyclonropvl)-?-naphthalenecarboYimidamide monoftrifluoroacetate)(salt) Example 97A
Copper (I) chloride (43 mg, 0.4 mmol), powdered zinc (26 mg, 0.4 mmol) were suspended in 1 mL dioxane for 18 hours. The product from Example 41 B (60 mg, U.2 mmoi) 25 was added and stirred and heated at 95 °C for 2() hours. The reaction mixture was concentrated on silica gel and purified by silica gel chromatography to give the desired compound.
MS (DCI/NH3) tn/z (M+NH;;)+ 287.
Exam Ip a ~7B
3U 6-(2-nhenvl-I-cvclooropvll-2-naphthalenecarbo~cimidamide monoltrifluoroacetate)(salt) The above was prepared from Example 1 using method from Example 1B.
MS (DCI/NH3) m/z (M+H)+ 287;

SUBSTITUTE SHEET (RULE 26) ~H-NMR (300 MHz. DMSO-d~) 8 9.41 (s, 2H), 9.16 (s, 2H), 8.46 (s, 1H), 7.83 (d, 2H), 7.62 (s. I H), 7.58 (dd, 1 H), 7.34 (dd, 1 H), 7.35-7.29 (m, 3H), 7.25-7.17 (m, 2H) 2.38-2.28 (m, 2H), 1.61 (t, 2H);
Anal. calc'd for C22H19N202F3 1/10 TFA: C, 65.00; H, 4.70; N, 6.84. Found: C, 65.22: H, 5.23; N, 5.10.
Example 98 (E)-6-f 2-(4-(aminomethyl)nhenyllethenvll-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) Example 98A
The desired compound was prepared using ethene under 500 atm pressure in a manner;
Analagous to that of Example 4I A.
MS (DCI/NH3) m/z (M+NH~)+ 197.
Example 98B
4- (Aminomethyl)-iodobenzene hydrochloride ( 1 g, 3.7 mmol) and Boc anhydride ( l .22 g, 5.6 mmol) were mixed with l U~7o NaOH ( 15 cnL), ethyl acetate (20 mL) and stirred 2 hours.
The organic; layer was washed with 5% sodium bicarbonate (2x, 10 mL), dried (magnesium 2U sulfate), and concentrated to give I .22 g of desired compound.
MS (DCI/NH3) m/z (M+NH3)+ 351.
Example 98C
The desired compound was prepared using the product from Example s 98A and 98B
in a manner analagous to that of Example 41 A.
MS (DCI/NH3) m/z (M+NH3)+ 4()2.
Example 98D
(E)-6-l2-f4-(aminomethvl)phenyl lethenyll-2-naphthalenecarboximidamide bis(trifluoroacetate)(Salt) The above product was prepared in a manner analogous to that of Example 40D
with the addition of trifluoroacetic acid in methylene chloride to remove the Boc group.
MS (DCI/NH3) m/z (M+H)+ 302;

SUBSTITUTE SHEET (RULE 26) I H-NMR (300 MHz, DMSO-d~,) 8 9.43 (s. 2H), 9. I 1 (s, 2H), 8.46 (s, 1 H), 8.16 (br, 3H}, 8.15 (d. 1 H), 8.04 (d, I H), 7.82 (dd, 1 H}, 7.75 (d, I H), 7.54 (s, 1 H) 7.50 (d, 1 H), 4.08 (d, 2H);
Anal. calc'd for C24H21N304F62/5 TFA: C. 50.46; H, 3.63; N, 6.99. Found: C;
50.37; H, s 3.86; N, 7.05.
Example 99 methvl 17-(aminoiminomethvl)-2-methoxy-1-naphthalenvl )carbamate mono(trifluoroacetate)(salt) 1 The desired compound was prepared using material prepared as described in Example 90D and utilizing the procedures described in Example 9I A and Example 40D.
MS (DCUNH3) m/z (M+H)+ 306;
~H-NMR (300 MHz, DMSO-d~,) 8 9.33 (s, 2H), 8.98 (s, 2H), 8.63 (s, 1H), 7.99 (d, 1H), 7.60 (dd. 1 H), 7.58 (s, 1 H), 7.54 (d, 1 H), 7.35-7.20 (m, 5H ), 4.52 (s, 2H);
I S Anal. calc'd for CZ 1 H2t~N3O3F3 13/5 TFA: C, 44.03; H, 3. I 9: N, 5.89.
Found: C; 43.97: H, 3.55: N. f~.1 ().
Example 100 7-methoxv-8-(2-pvrimidinylamino)-2-naphthalenecarboximidamide bisltrifluoroacetate)(salt) 2U The desired compound was prepared using material prepared as described in Example 90D and utilizing the procedures described in Example 91 A and Example 40D.
MS (DCI/NH3) m/z (M+H)+ 322;
IH-NMR (300 MHz, DMSO-d~,) b 9.35 (s, 2H), 8.90 (s, 2H), 8.34 (s, 1H), 8.1 I
(d, 1H), 7.90 (d, 1H), 7.72 (d, 1H), 7.60 (dd. 1H), 7.47 (s, 2H), 6.70 (d, 2H) 6.49 (d.
2H), 3.~8 (s, '?, _3H), 3.64 (s, 3H);
Anal. calc:'d for C~ I H2~~N,;04F~ 1 /1 () TFA: C, 56.90: H, 4.53; N, 9.38.
Found: C; 56.88; H, 4.41; N, 9.43.
Example 101 3(> 7-methoxv-8-((phenvlmethvllaminol-~-naphthalenecarboximidamide monoftrifluoroacetate)(salt) Example 1 () l A

SUBSTITUTE SHEET (RULE 26) WO 99105096 PCT/US9811538( 4-Bromostyrene (4.8 g, 26.2 mmol) was dissolved in 100 mL THF and cooled to -°C. Butyl lithium (2.5 M in hexanes. 28.8 mmol) was added dropwise and stirred 5 minutes.
Iodine in THF was added dropwise until an orange/red color persisted.
Concentrated aqueous ammonium chloride (20 mL) was added and the reaction was warmed to room temperature, s diluted with ether, washed with 10~o Na2S205 solution ( 1 x, 50 mL), and brine ( 1 x, 50. mL), dried (magnesium sulfatej, and concentrated to give the desired compound.
MS (DCI/NH3) m/z 122.
Exam le 1 I B
m The product from I()4A (2.35 g, 10.2 mmol), 1.6 mL 60°l0, N-methylmorphiline-N-oxide/water solution, 3.75 mL acetone, 0.1 mL water were stirred 1 hour. 20 mL
Osmium ten-oxide/tert-butanol solution (0.02 mmol/mL} was added and stirred at 0 °C for 20 hours. The reaction was concentrated on silica gel and purified by silica gel chromatography to give the desired compound.
t, MS (DCI/NH3) m/z (M+NH~)+ 282.
Example 101 C
The desired compound from Example 104B is coupled using Method 41A.
MS (DCI/NH3) m/z (M+NH3)+ 333.
2Il Example 1 O 1 D
7-methoxv-8-((phenvlmethyl)aminol-~-n~phthalenecarborimidamide mono(trifluoroacetate)lsalt) The above was prepared from Example 104C using method described in Example 40D.
?5 MS (DCI/NH3) m/z (M+H)+ 333;
~ H-NMR (300 MHz, DMSO-d~) 8 9.42 (s, 2H), 9.12 (s, 2H), 8.45 (s, 1 H), 8.15-8.05 (m, 4H), 7.81 (dd, lHj, 7.63 (d, 2H), 7.48 (d, 2H), 7.39 (d, 2H), 4.56 (t, IH), 3.45 (d, 2H);
Anal. calc'd for C23H21N204F3 2/5 TFA: C, 58.19; H, 4.39; N, 5.71. Found: C, 58.17; H, 4.41; N, 5.87.
3c~
Example 102 7-methoxv-8-(nhenvlamino)-~-naohthaIenecarboximidamide monoltrifluoroacetate)lsaIt) Exam In a 102A

SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCT/US981I5386 Ten-butylcarbamate (3.62 g, 15.7 mmol) was dissolved in 63 mL propanol. I I 8 mL
NaOH/water solution (0.4 N), tej-t-butyl hypochlorite (5.5 mL, 47.8 mmol). and (DHQD)2PHAL (612 mg, 0.63 mmol) in 50 mL propanol were added and stirred 10 minutes.
The product from Example 2 (3.62 g, I5.7 mmol}, and KZOs04~2 water (211 mg, 0.63 mmol) S were added and stirred 24 hours. The reaction was concentrated and recrystallized from ethanol/hexanes to give the desired compound.
MS (DCI/NH3} m/z (M+NH3)+ 3H 1.
Example 102B
The above was prepared from Example t02 using the method described in Example 41 A.
MS (DCI/NH3) m/z (M+H)+ 415 Example 102C
is 7-methoxv-H-(Dhenvlamino)-2-naohthalenecarboximidamide mono~trifluoroacetate)lsalt) The above was prepared from Example 102B using the method described in Example 94D.
MS (DCI/NH3) m/z (M+H)+ 264;
~ H-NMR (3(l() MHz, DMSO-d6) 8 9.42 (s, 2H), 9.07 (s, 2H), R.45 (s, 1 H), 8.33 (br, 3H), 2~~ H.16-8.03 (m, 4H) 7.75 (d, ZH), 7.56 (s, 2H), 7.49 (d, 2H), 5.49 {br 1 h), 4.2X (br 1H), 3.62 (m, 2H};
Anal. calc'd for C~5H23N~OSF~,~S TFA: C, 37.30; H, 2.51; N, 3.74. Found: C;
37.06; H, 3.12; N, 4.42.
'S Example I()3 7-methoxv-h-f (4-metho~cyphenyl)amino!-2-naphthalenecarboximidamide mono(trifluoroacetate)lsalt) Example 103A
3U 4-Bromobenzaldehyde (600 mg, 3.24 mmol), 16.2 mL dimethylamine in THF (32.4 mmol), and sodium triacetoxyborohydride (I.24 g, 5.S mmol) were suspended in dichloroethane ( t 0 mL). The reaction mixture was concentrated, diluted with water acidified to pH=2 and extracted with ether (3x, 20 mL). The aqueous solution was basified with SUBSTITUTE SHEET (RULE 26j NaOH/water to pH=12 and extracted with methylene chloride (3x, 30 mL, acidified with HCI/methanol and concentrated to give the desired compund.
MS (DCI/I~fH3) m/z (M)+ 214.
Example 103B
The above was prepared from Example 107A using method from Example 4IA.
MS (DCI/NH3) m/z (M+H)+ 313.
Example 103C
l t) 7-methoxv-8-I(4-methoxyphenyllamino 1-~-nanhthalenecarboximidamide mono(trifluoroacetatel(salt) The above was prepared from Example 103 using method from Example 40D.
MS (DCI/NH3) m/z (M+H)+ 294;
iH-NMR (300 MHz, DMSO-d~,) 8 9.43 (s, 2H}, 9.11 (s, 2H), 8.46 (s, IH), 8.18-8.06 (m, t5 4H), 7.H4 (d, 4I-I), 7.60 (s, 2H), 7.56 (s, 1H), 4.53 (s, 2H), 3.05 (s, 6H);
Anal. calc'd for C2~,H25N304F~ 7/5 TFA: C, 4)i.46; H, 3.73; N, 5.91. Found: C, 48.36; H, 4.25; N, 6.19.
Exam le 1 )4 20 (E)-t~-f2-f4-(1, 2-dihdvroxveth~phenyllethenyll-~-naohthalenecarboximidamide mono(trif3uoroacetate)lsalt) Example 104A
The above was prepared from 4-bromobenzyl alcohol and the compound prepared in 25 Example 9~iA using the method from Example 41 A.
MS (DCl/NH3) m/z (M+NH3)-~ 303.
Example 104B
(E)-6-f2-f4-(1, 2-dihdvroxvethyl)phenyl ethenyll-2-naphthalenecarboximidamide_, 3O mono(trifluoroacetate)(salt) The above was prepared from Example 104A using method from Example 40D.
MS (DCI/NH3) m/z (M+H)+ 303;
t H-NMR (300 MHz, DMSO-d6) 8 9.00 (br, 4H}, 8.44 (s, 1 H), 8.15-8.01 {m, 4H), 7.81 (dd, 1 H), 7.64 (d, 2I-i), 7.48 (d, 1 H), 7.36 (d, 2H), 5.21 (br, I N) 4.53 (s, 2H);

SUBSTITUTE SHEET (RULE 26) WO 99105096 _ PCT/US98115386 Anal. calc'd for C?2Ht9N203F3 4/5 TFA: C, 55.84; H, 3.93; N, 5.52. Found: C, 55.60; H, 3.93; N, 6.41.
Example 105 S (E)-6-f2-f4-(1R-amino-2-hvdroxveth~,~henyll then ly_1-2-naohthalenecarborimidamide bis(trifluoroacetate)(salt~, Example 105A
Using the procedure described for Example 121 A, and substituting N-BOC-p-lt) iodophenylalanine (BACHEM Bioscience Inc.} for 4-iodoaniline, the desired compound was obtained.
MS {DCI/NH3) m/z 458 (M+NH4)+;
tH NMR (300 MHz, CDC13) 8 1.35 (s, 9H), 2.9() (t, 1H), 3.09 (dd, 1H), 4.15 (m, IH), 7.20 td, 1H), 7.36 (d, 2H). 7.56 (d, 2H), 7.78 (d, 1H), 7.X5 (d, 1H), 8.12 (d, 1H), 8.17 (d, lHj, 15 8.32 (s, 1H), 8.62 (s, 1H).
Example 105B
Using the product obtained in Example 105A and the procedure described in Example 40D the desired compound was obtained.
2t~ MS (ESI) m/z 458 (M+H)+;
~ H NMR (300 MHz, DMSO} 8 I .35 (s, 9H}, 2.90 (dd, 1 H), 3.10 (dd, 1 H), 4.13 (m, 1 H), 7.10 (d, 1 H), 7.36 (d, 2H}, 7.55 (d, 2H), 7.78 (dd, 1 H}, 7.85 (dd, 1 H), 8.13 (d, 1 H), 8.19 (d, 1 H), 8.30 (s, 1 H), 8.50 (s, I H), 9.22 (s, 2H), 9.42 (s, 2H).
'S Example 105C
IE)-6-12-f4-( 1 R-amino-2-hvdroxvethvl)phenvl lethenyl l-~-naphthalenecarboximidamide bis(triouoroacetate)(sal~
Using the product obtained in Example 1()5B and the procedure described for Example 124D, the desired compound was obtained.
3o MS (ESI) m/z 358 (M+H)+;
t H NMR (300 MHz, DMSO) b 3.(12 (m, I H), 3.19 (dd, 1 H), 3.63 (t, 1 H), 7.39 (d, 2H), 7.58 (d, 2H), 7.76 (d, l H), 7.88 (d, 1 H), 8.15 (d, I H), 8.19 (d, lHj, 8.30 (s, 1 H), 8.51 (s, 1 H), 9.41 (s, 2H), 9.80 (s, 2H);

SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCTJUS9811538~
Anal. calc'd for C2q.H2~F3N304~H20: C, 58.90; H. 4.53; N, 8.59. Found: C, 58.75: H. 4.22;
N, 8.28.
Example 106 S 7-methoxv-R-(2-pvrimidinylamino)-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) Example I06A
Sodium borohydride (0.22 g, 5.8 mmol) was added to a suspension of (4-bromobenzoyl)methanol (2.5 g, 11.6 mmol, Maybridge Chem. Co.) and 25 mL abs.
ethanol.
1u The reaction mixture was stirred at reflux for 1 hour. After cooling to room temperature, the ethanol was evaporated under vacuum, and water was added to the residue. The mixture was extracted with CH2Cl2. The extracts were washed with saturated aqueous sodium chloride, dried over MgS04, filtered, and evaporated under vacuum to afford the desired compound.
MS (DCI/NH3) m/z 234/236 (M+NH4)+;
o s ~ H NMR (3()0 MHz, CDCl3) 8 2.10 (t, 1 H), 2.62 (d, 1 H ), 3.63 (m, 1 H}, 3.78 (m, 1 H), 4.81 (m, 1 H), 7.25 (d, 2H), 7.50 (d, 2H).
Example 106B
Using the product obtained in Example 106A and the procdure described in Example A-2U 22621?i-A, the desired compound was obtained.
MS (DCl/NH3) m/z 331 (M+NH4)+;
~ H NMR (300 MHz, CDC13) 43.45 (t, I H}, 4.59 (q, 1 H), 4.76 (t, 1 H), 5.36 (d, 1 H), 7.42 {d, ZH), 7.59 (d, 2H), 7.78 (dd, 1 H), 7.85 (dd. 1 H), !x.10 (d, 1 H), 8.15 (d, 1 H}, 8.30 (s, 1 H), 8.61 (s, 1 H).
2;
Example 1 ()6C
7-methoxv-8-(2-pvrimidinylamino)-2-naphthalenecarboximidamide bis(trifluoroacetate)falt) Using the product obtained in Example 106B, and the procedure described in Example 40D, the desired compound was obtained.
aU MS (ESI) m/z 331 (M+H)+;
~H NMR (3()0 MHz, DMSOj S 3.45 (t, 1H), 4.59 (q, IH), 4.7R (t, 1H), 5.38 (d, 1H), 7.42 (d, 2H), 7.59 (d, 2H), 7.78 (dd, 1 H), 7.84 (dd, 1 H), $. I 2 (d, I Hj, 8.18 (d, 1 H), 8.31 (s, I H), 8.50 (s, 1 H}, 9.20 (s, 2H), 9.43 (s, 2H);

SUBSTITUTE SHEET (RULE 26) Anal. calc'd for C2~HJ9F~N204~H20: C, 59.74; H, 4.SH; N, 6.06. Found: C, 59.95; H, 4.I7;
N, 6.13.
Example 107 s (E)-~-I2-II4-(dimethvlamino)methyl~phenyrllethen 1 -~-naphthalenecarboximidamide bis(trifluoroacetate)(salt~
Example IO7A
Using the procedure described for Example I2IA, and substituting 3-m benzyloxybromobenzene CChem. Ber.124 ( 1 ), 163, 1991 ) for 4-iodoaniline, the desired compound was obtained.
MS (DCI/NH3) m/z 377 (M+NH4)+;
J H NMR (3()O MHz, CDCl3) 8 5.1 I (s, 2H), 7.()2 (d, 1 H), 7.20 (m, 2H), 7.29 (d, 1 H), 7.31 (d, IH), 7.42 (m, 3H), 7.60-7.75 (m, 3H}, 7.H9 (t, 2H), H.()S (s, 1H), H.21 (s, IH).
Example 1 (77B
(E)-6-12-114-(dimethvlamino)meth~lphenyl ethenyl-!-~-naphthalenecarboximidamide bis(trifluoroacetate)(saIt~
Using the product obtained in Example 1()8B, and the procedure described in Example 20 4UD, the desired compound was obtained.
MS (ESI) m/z 377 (M+H)+;
) H NMR (3()0 MHz, D MSO) 8 5. I 8 (S, 2H), 7.12 (dd, 1 H), 7.22 (d, 1 H), 7.2$ (m, 1 H), 7.4(J (t, 3H), 7.45 (t, 3H), 7.79 (dd, 1H), 7.H5 (dd, IH), H.16 (d, 1H), x.20 (d, IH), H.35 (s, 1H), H.5(J (s, 1H), 9. 3(J (s, 1H);
?5 Anal. calc'd for C~~H21F~N~03~().25 HBO: C, 67.94; H, 4.3H; N, 5.66. Found:
C, 67.H(); H, 4.4K; N, 5.43.
Example 1 ()S
(E)-6-f 2-I4-(hvdroxymethvl)phenvl lethenvl l-2-na~phthalenecarboximidamide ~~) mono(trifluoroacetate)(salt) Using the product obtained in Example I08A and the procedure described in Example 94D the desired compound was obtained.
MS (ESI) m/z 2R7 (M+H)+;

SUBSTITUTE SHEET (RULE 2fi) ~ H NMR (300 MHz, DMSO) 8 6.89 (m, I H), 6.98 (t, 1 H), 7.03 (d, 1 H), 7.29 (t. 1 H), 7.78 (dd, IH), 7.88 (dd, 1H), 8.13 (d, 1H), 8.I7 (d, 1H), 8.32 (s, 1H). 8.50 (s.
1H), 9.40 (s, SH);
Anal. calc'd for C~iHtSF3N~03~().5 H20: C, 61.62; H, 3.94; N, 6.84. Found: C, 61.29; H, 3.8I; N, 6.59.
Example 109 4-f I6-(aminoiminomethyl)-2-naphthalenyllethynvll-L-phenylalanine mono(trifluoroacetate)(salt) 1u Example 109A
To a solution of the product from Example 8D (2.13 g, 10.08 mmol> and LiBH4 (121 mg, 5.55 mmol) in THF (5 mL) was added toluene (2 mL), and the THF was boiled off using a short-path distillation apparatus over several hours. The reaction was then heated at 70°C for 2 n hours, cooled, quenched with 1 M HCI, and extracted with 2x ethyl acetate.
The extracts were washed with water and brine, dried over Na~S04, and condensed. The crude product was chromatographed on Si02 using SO~Io ethyl acetate/hexanes as eluent, to yield 1.12 g (6I%) of the desired compound.
MS (DCI (NH3)) m/z 201 (M+NH4)+;
20 ~ H NMR (300 MHz, CDC13) 8 8.22 (s, 1 H), 7.90 (m, 3Hj, 7.61 (m, 2H), 4.92 (d, 2H), 1.84 (t, 1H).
Exam,.ple 109B
To a solution of the product from Example 109A (2.I2 g, I 1.57 mmol) and Liar (1.1 1 5 g, 12.73 mmol) in DMF ( 1()0 mL) was added PBr3 ( 1.21 mL, 12.73 mmoi) at 0°C, and the reaction was warmed to room temperature, and stirred for 1 hours. The reaction was then duenched with pl-I 7 buffer, and extracted with 3x diethyl ether/hexanes. The extracts were washed with 2x water and 2x brine, dried over Na~S04, and condensed, to yield 2.72 g (96%) of the desired compound.
3o MS (DCI (NH3)) m/z 185 (M+NH4-gr)+;
1 H NMR (30(1 MHz, CDCl3) S 8.22 (s, I H), 7.92 (s, 1 H), 7.9() (s, 2H), 7.62 (dd, 2H), 4.64 (s, 2H).
Example 109C

SUBSTITUTE SHEET (RULE 26) To a solution of NaH (60~1o in mineral oil, 44 mg, 1. I mmol) in DMF (5 mL) was added 4-ethylphenol ( 122 mg, 1.0 mmol j, and the reaction was stirred at room temperature for 20 minutes. The product from Example 109B (270 mg, 1.1 mmol) was then added, and the reaction was stirred for 10 minutes. The crude reaction mixture was chromatographed on Si02 :: using hexanes as eluent, to yield 220 mg (77%) of the desired compound.
MS (DCl (NH3)) m/z 305 (M+NH4)+;
~ H NMR (300 MHz, CDC13) 8 $.22 (s, 1 H), 7.95 (s, 1 H), 7.93 (s, 1 H), 7.91 (s, 1 H), 7.66 (dd, 1H), 7.61 (dd, 1H), 7.15 (d, 2H), 6.94 (d, 2H), 5.22 (d, 2Hj, 2.60 (q, 2H), 1.21 (t, 3H).
Example 109D
4-If6-(aminoiminometh 1)-2-na hthalen~lleth5rn I~l-L-,phenvlalanine r~r ono(trifluoroacetat )lsalt~
The desired compound was prepared from Example 109C and the procedure of Example is 55D.
MS (DCI/NH3) m/z 305 (M+H)+;
~H NMR (30() MHz, DMSO-d~,) 8 1.15 (t. 3H), 2.14 (s, 3Hj, 2.56 (q, 2H), 5.30 (s, 2H), 6.9?S (d, 2H), 7.14 (d, 2H}, 7.74 (dd, 1 H), 7.H2 (dd, 1 H), H.15 (m, 3H), H.4S (s, 1 H}, 9_.01 (br s, 2H), 9.62 (br s, 2H);
2n Anal. valc'd for C2pH2pN20~1.4 CH4S03: C, 58.56; H, S.SS; N, 6.3K. Found:
C, 5H.55; H, 5.56; N, 6.39.
Example 1 1 1 6-(3-formviohenvl)-2-nanhthalenecarboximidamide mono(trifluoroacetate)(salt) Example 1 1 1 A
The product from Example 2$B (334 mg, 1.1 1 mmol j, palladium acetate (25 mg, 0.1 1 mmol), dppf (123 mg, 0.22 mmol) were dissolved in degassed DMF (5 mLj and stirred at room temperature for 1/2 hour. Cesium carbonate (902 mg, 2.H mmol) and 2-3o formylphenylboronic acid (251 mg, 1.27 mmol) were added and stirred under nitrogen at RO °C
for I hour, poured into pH 7 buffer, extrated with diethyl ether (3x, 20 mL), and dried. The desired compound was purified by chromotography eluting with 10~'/o ethyl acetate/ hexanes.
MS (DCI/NH3) m/z (M+NH3)+ 275.

SUBSTITUTE SHEET (RULE 26) Example 1 1 1 B
6-f3-formvl~henvl)-2-nar?hthalenecarboximidamide mono(trifluoroacetarP)fealt) The above product was prepared in a manner analogous to that of Example IB.
MS (DCI/NH3) m/z (M+H)+ 274;
s ~ H-NMR (300 MHz, DMSO-d~,) b 10.16 (s, 1 H}, 9.47 (s, 2H), 9.10 (s, 2H), 8.54 (s, I Hj, 8.52 (s, 1 H), 8.41 (s, 1 H), 8.28-8.23 (m, 3H), 8.12 (dd, 1 H), 8.00 (dd, 1 H), 7.87 (dd, 1 H), 7.80 (t. 1 H);
Anal. calc'd for C2~)HISN~03F3 2/5 TFA: C, 59.28: H, 3.70; N, 6.34. Found: C;
59.36; H, 3.89; N, 7.21.
Examl 1~ a I 12 (E)-6-f2-(1 ~ 3 4-tetrahydro-6-isoquinolin 1 a h n_yll-2-naphthalenecarboximidami a ~sltrifluoroacetate)(,~alt) Example 1 12A
The above was prepared from Example 127 using method described in Example 41 A.
MS (DCI/NH3} m/z (M+H)+411.
Example 1 12B
20 (E)-6-f2-(1. 2, 3. 4-tetrahvdro-6-isoduinolin 1)teethe,nyll-~-naphthalenecarboximidamide bisltrifluoroacetate)(salt) The desired compound was prepared by the method described in Example 40D.
MS (DCI/NH3) m/z (M+H)+ 328;
~ H-NMR (300 MHz, DMSO-d~,) 8 9.36 (s> 2H), 9.25 (s, 2H), 9.10 (d, 2H), 8.41 (s, I H), ?5 7.99 (t. 2H). 7.89 (d, IH), 7.7H (d, IH), 7.71 (dd, 1H), 7.56 {m. 4H). 7.43 (s, 1H), 3.11 (br, 2H) 2.16 (br 2H), 1.78 (br, 2H);
Anal. calv'd for C2~,H23N304Fr, 3/5 TFA: C, 52.31; H, 3.1i 1; N, 6.72. Found:
C, 52.13; H, 4.42; N, 7.23.
ExamrJle 113 (E)- 6-f2-f3-(2-hvdroxvethvl)phenyllethenyll-2-naphthalenecarboximidamid mono(trifluoroacetatel(salt) Example 1 13A

SUBSTITUTE SHEET (RULE 26) The above was prepared from 2-bromo-3 (hydroxyethyl)alcohol and the compound prepared in Example 98A using method described in Example 41 A.
MS (DCI/NH3) m/z (M+NH3)+ 317.
Example I 13B
(E)- 6-12-f3-!2-hvdroxvethvl) henvllethenyl -~-na hoo thalenecarboximidamide monoltrifluoroacetate)lsaltl The above was prepared from Example 1 13A using method described in Example 40D.
MS (DCI/NH~) m/z (M+H)+ 3I7;
n> >H-NMR (300 MHz, DMSO-d~,) 8 8.9 (br, 4H), 8.46 (s, IH), 8.17 (s, IH), 8.I3-8.03 (m, 3H), 7.H2 (dd, 1 H), 7.54 (s, 2H), 7.49 (s, 2H), 7.33 (t, 1 H) 7.1 H {d. I H), 4.71 (t, I H), 3.66 (m, 2H), 2.7$ (t, 2H);
Anal. calc'd for C23H~1 N203F3 3/10 TFA: C, 61.41; H, 4.66; N, 6.09. Found: C, 64. l Ii; H, 4.92; N, C~.51.
IS
Example 114 h-laminoiminomethvl)-4-!~i-furanvl)-N-14-ltrifluoromethyllphenvll 2 n~hthalenec.arboxamide mono( trifluoroacetate)(salt) 't~ Example 1 14A
The product from Example 152B (100 rng, (1.36 mmol), 4-(trifluoromethyl)aniline {86 rng, 0.53 mmol), and DMAP (5 mg, 0.04 mmol) were dissolved in THF (5 mL) and stirred for 24 hours. The reacaion mixture was concentrated on silica gel and purified by chromotography (Biotage Flash 40) using ethyl acetate/hexanes.
25 MS (ESI) m/z (M+H)+4()f~.
Exam~e I 14B
fi-(aminoiminomethvl)-4-!'i-furanvl)-N-f4-(trifluorometh~~phenyll 2 nanhthalenecarboramide mono(trifluoroacetate)ls It) The above was prepared from Example I 14A using method described in Example 1 B.
MS (CI) m/z (M+H)+ 424;

SUBSTITUTE SHEET (RULE 26) 1 H-NMR (300 MHz, DMSO-d~,) b 10.91 (s, I H), 9.51 (s, 2H). 9.1 1 ( s, 2H), 8.69 (s, I H), H.62 (s, 1 H), 8.43-8.35 (m, 2H), R.1 S (d, 1 H), X.06 (d. 2H), 7.911 (t. 1 H), 7.92 (dd, 1H), 7.78 (dd, 2H) 7.14 (m, 1 H);
Anal. caIc'd for C25HI7N304F~ 1/10 TFA: C, 55.37; H, 3.15; N, 7.70. Found: C, 55.44; H, s 3.15; N, 7.31.
Example 115 6-(atninoiminomethvl)-4-(3-furanyl )-N-(4-pyridinvl)-~-naphthalenecarboxamide dihvdrochloride Example 1 15A
The above product was prepared in the manner of Example 114A.
MS (ESI) m/z (M+H)+ 340.
I S Example 1 I SB
6-(aminoiminomethvl)-4-(3-furanyl)-N-(4-pvridin l)-~-naphthalenecarboxamide dihydrochloride The above was prepared from Example 1 1 SA using method described in Example 1 B.
MS (AP/CI) m/z (M+H)+ 357;
2c> I H-NMR (300 MHz, DMSO-d~,) 8 12.43 (s. 1 H), 9.69 (s, 2H), 9.40 (s, ZI-i), 8.94 (s, 1 H), H.H I (d, 2H), 8.65 (s, 1 H), B.SH-H.56 (m, 2Hj, 8.49 (s, 1 H), 8.42 (d, 1 H), 8.30 (m, 1 H) 7.97-7.95 (m, 2H), 7.27 (s, I H);
Anal. calc'd for C~~H1gN40~C12 37/IO HCI: C, 44.65 H, 3.88 N, 9.92. Found: C, 44.72: H, 3.70: N, 9.51.

Example 1 16 6-(aminoiminomethyl)-4-l3-furanvl)-N-( 1 H-pyrazol-~ yl) 2 naphthalenecarboxamide dihydrochloride Example I 16A
The above product was prepared in the manner of Example 1 14A.
MS (ESIj m/z (M+H)+ 329.
Example 1 I6B
-t35-SUBSTITUTE SHEET (RULE 26) 6-(aminoiminomethvl)-4-('~-furanvl)-N-( 1 H-~yrazol-'~-vl)-2-naphthalenecarboxamide dihydrochloride The above was prepared from Example I I6A using method described in Example I
B.
MS (CI) m/z (M-H)+ 344;
1 H-NMR (300 MHz, DMSO-d6) b i I .16 (s, 1 H), 9.52 (s, 2H), 9.10 (s, 2H), 8.69 {s, i H), 8.61 (s, 1H), 8.35 (m, 2H), 8.24 (s, IH), 7.96-7.88 (m, 3Hj, 7.69 (m, IH), 7.15 (s, IH) 6.69 (m, 1 H):
Anal. calc'd for C(9H(7N502C12 9/10 HC1: C. 50.63; H, 4.00; N, 15.54. Found:
C, 51.()5;
H, 4.62; N, 14.26.
Examl 1~ a I 17 6-(aminoiminomethvl )-4-(3-furanyl )-N-(3-pyridinyl l-2-nanhthalenecarboxamide dihydrochloride Example 117A
The above product was prepared in the manner of Example 1 14A.
MS (ESI) m/z (M+H)+ 340.
Example l I7B
2U 6-(aminoiminomethvl)-4-(3-furanyll-N-(3-pyridin l~-2-na-phthalenecarboxamide dihydrochloride The above was prepared from Example 1 17B using method described in Example 1 B.
MS (C1 ) m/z ( M+H )+ 357;
~H-NMR (3()0 MHz, DMSO-df,) b 1().9() (s, IH), 9.59 (s, 2H), 9.26 (s, 2H), 9.03 (s, 2H), 25 h.74 (s, 1 H). ?S.F~3 (s, 1 H), H.42-8.2f~ (m, 3I-I), 8.22 (s, lI-I), 7.97-7.91 (m, 2H), 7.47-7.43 (m, 2H), 7.17 (s, 1H);
Anal. calc'd for C21H1~N4O2C12 55/1() HCI: C, 40.00 H, 3.76 N, 8.89. Found: C, 40.09; H, 3.78; N, 8.44.
-t« Example 118 6-(aminoiminomethvl)-N-(2 ~-dihydro-1H-inden 5 yl) 2 naphthalenecarboxamide mono(trifluoroacetate)(salt) Example 1 18A

SUBSTITUTE SHEET (RULE 26) To a solution of the compound prepared in Example SE (303 mg, 1.4 mmol) in THF
(30 mL) and propylene oxide ( I S mL) was added two drops of Et3N followed by the 5-aminoindene (300 mg, 2.2 mmol). The reaction was stirred at room temperature overnight. The solvent was evaporated and the product was purified via crystallization from ether to yield 226 S mg (S6%) of the product as white solid. Mass spectrum (CI+), 313 (M+1 )+.
Example I I8B
6-(aminoiminomethvll-N-(2 'i-dihydro-IH-inden-S-vI)-~-nay~hthalenecarboxamid~P
mono(trifluoroacetate)( ~It) The compound prepared in Example 118A {20S mg, 0.66 mmol) in THF (20 mL) at room temperature, was added butyl lithium ( 1 mL, 1 mmol) followed by chlorotrimethyl silane ( 180p.L, 1.S mmol). After i0 minutes the mixture was charged with additional butyl lithium (3 mL, 3 mmol). The reaction was stirred at room temperature, overnight. The reaction mixture was added a solution of 4 N HCl in dioxane stirred far an hour then added water and n evaporated. The product was purified by MPLC RP CIA with methanol-water and 0.1% TFA as eluent chromatography. The yield of the product as TFA salt with 0.25%c water as white solid S 1 mg ( 17 %).
MS (ESI+) 330 (M+I)+;
~ H NMR (DMSO-d6) 1 ().45 (s, 1 H), 9.S 1 (s, 2H), 9.21 (s, 2H), 8.66 (s, 1 H), B.SS (s, I H), 2U 8.32 (d, J=B.SHz, 1H), 8.20 (Abq, J=9.OHz, 2H), 7.90 (dd, Jl=9.0Hz, J~=I.SHz, 1H), 7.73 (s, 1H), 7.53 (dd, J(=8.0Hz, J2=I.SHz, IH), 7.22 (d, J=8.lHz, IH), 2.91-2.82 (m, 4H), 2.04 (quintet, J=7.3Hz, 2H);
Anal. calc'd for C21H1yN~O~TFA~0.2S H20 C: 61.67; H, 4.61; N, 9.38. Found: C:
61.63; H, 4.43; N, ~J.2S.
,5 Example I 19 methyl .5-I7-f(aminoiminomethvl)-~-naphthalen lv lorylpentanoate mono(trifluoroac;etate~ (salt) Example 1 19A
J« 7-hvdroxy-2-cyanonaphthalene 7-methoxy-2-cyanonaphthalene (2.79 g, 5.23 mmol) and tetrabutylammonium iodide ( 17 mg, 0.157 mmol) were combined in a mixture of benzene (3S mL) and cyclohexanes ( 17.5 mL). The resulting solution was added to a rapidly stirring, cooled (ice/water) suspension of aluminum triiodide (6.21 g, 15.23 mmol) in a mixture of benzene (3S mL) and cyclohexanes SUBSTITUTE SHEET (RULE 26) WO 99105096 , PCTlUS98/15386 ( 17.5 mL) under an inert atmosphere. After the addition, the resulting suspension was heated at reflux for 2.5 hours. The heating was removed and after cooling to near room temperature, the reaction mixture was cooled in an ice bath and quenched by the addition of water ( l0U mL). The resulting mixture was further diluted with 2 M aqueous sodium thiosulfate solution (50 mL) and S extracted with ethyl acetate (3 X 80 mL). The combined organic layers were dried and evaporated. The resulting solid was dissolved in a minimum of hot ethyl acetate, diluted hot with hexanes to the cloud point and placed in a refrigerator for 2 hours. The desired compound was collected by filtration, ( 1.99 g, 77% ).
MS (DCI (NH3)) mJz 187 (M+NH4)+.
Example 119B
The resulting product from Example 1 19A was treated with methyl 5-bromovalerate in an analogous manner as described in Example 1 19A.
~'~S (DCI (NH3)) m/z 3()1 (M+NH4)+.
IS
Example 1 19C
methyl 5-f 7-f (aminoiminomethyl)-2-nal hthalenyllox~pentanoate mono(trifluoroacetate) (salt) The resulting product from Example 1 19B (3X0 mg, 1.3412 mmol) was treated in an analogous manner as described in Example 94D to yield the desired compound (369 mg, 73°l0).
2o MS (DC1 (NH3)) tn/z 301 (M+H)+;
1H NMR (300 MHz, DMSO-d6) b 1.7X5 (m, 4H), 2.425 (t, 2H), 3.600 (s, 3H), 4.150 (t, 2H}, 7.3RC) (dd, 1 H), 7.46() (d, 1 H), 7.640 (dd, 1 H), 7.9X0 (d, 1 H), K.070 (d, 1 H), 8.322 (d, 1 H), 9.230 (v br s, 3H);
Anal. calc'd for CpH2t~N~O~~C2HO~F~: C, 55.07; H, 5.1 l; N, 6.76. Found: C, 54.96; H, '_'S 5.2~: N. 6.66.
Example 120 (E)-3-17-(aminoiminomethyl)-2-methox -1-naphthalenyl) ~ propenamide mono(trifluoroacetate)(salt) 3«
Examlhe 120A
The product obtained from Example 53B and acrylamide were subjected to the conditions described in Example 41 A to provide the desired compound.
MS (DCI/NH3) m/z 253 (M+H)+.
-13k-SUBSTITUTE SHEET (RULE 26) Example 120B
(E)-3-f7-(aminoiminomethvl)-2-methox -~phthaleny~-2-propenamide mono(trifluoroacetate)(salt) s The product obtained from Example 120A was subjected to the conditions described in Example 94D to provide the desired compound.
MS (DCI/NH3) m/z 270 (M+H)+;
IH NMR (300 MHz, DMSO) 8 4.02 (s, 3H), 6.90 (d, IH), 7.22 (s, 1H), 7.62-7.70 (m, 2H), 7.74 (d, I H), 8.02 (d, l H), 8.1 1 (d, 1 H), 8.15 (d, I H), 8.58 (s, I H), 9.18 (s, 2H), 9.50 (s, m 2H);
Anal. calc'd for Cl7Ht~F3N304~H20: C, 50.88; H, 4.52; N, 10.47. Found: C, 50.89; H, 4.32; N, 10.43.
Exam 1 6-f(4-arninovhenvl)ethvnvll-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) IS
Example 121 A
A mixture of the product obtained in Example 63B (130 mg, 0.73 mrnol), 4-iodoaniline (173 mg, 0.79 mmol), dichlorobis (triphenylphosphine)palladium (II) (25 mg, ().0325 mmol), copper (I) iodide (2.7 mg, ().()I86 mmol), DMF (0.65 mL), and triethylamine (1.95 mL) was 2o degassed with N2 and was stirred at 75°-80° for 1.5 hour. The mixture was cooled to room temperature, diluted with CH2CI2, washed with water, dried (MgS04), filtered, and evaporated under vacuum to afford an oil which was purified by flash chromatography, eluting with 3: !
hexanes: ethyl acetate to afford the desired compound.
MS (DCI/NH~) m/z 269 (M+H)+.
?5 Example 121 B
fi-If4-aminophenvl)ethvnvll-2-naohthalenecarboximidamide bis(trif7uoroacetate?(salt) Using the product obtained in Example 121A and the procedure described in Example 40D, the desired compound was obtained.
3o MS (DCI/NH3) m/z 286 (M+H)+;
iH NMR (30U MHz, DMSO) 8 6.80 (d, 2H), 7.29 (d, 2H), 7.70 (dd, 1H), 7.X5 (dd, 1H), 8.09 (d, 1 H), 8.14 (d, 1 H), 8.20 (s, I H), 8.45 (s, 1 H), 9.09 {s, 2H), 9.42 (s, 2H);
Anal. calc'd for C23H17Fr,N~04~0.25 H20: C, 53.34; H, 3.41; N, 8.1 I. Found:
C. 53.45; H, 3.70; N, 7.76.

SUBSTITUTE SHEET (RULE 26) Example 122 1, 1-dimethvlethvl f2-f3-ff6-(aminoiminomethvIl-2-nanhathalenyllethvnyl]-f~
methoxwhenvllethyllcarbamate mono(trifluoroacetate)(sal~
Exam;r~le I22A
Using 5-bromo-2-methoxyphenethylamine hydrobromide (Transworld), and the procedure described in Example 63C, the desired compound was obtained.
MS (DCl/NH3) m/z 330 (M+H)+.
Example 1228 Using the procedure described for Example 12I A, and substituting the product obtained in Example 122A for 4-iodoaniline, the desired compound was obtained.
MS (ESI) m/z 427 (M+H)+.
Example 122C
l, I-dimethvlethyl f2-f3-ff6-(aminoiminomethyl)-2-n~hathalen I~lethynyll~fi methoxmhenvllethvllcarbamate mono(trifluoroacetate)(sal~
Using the product obtained in Example A-226638-B and the procedure described in 2c> Example 40-D, the desired compound was obtained.
MS (DCI/NH3) m/z 444 (M+H)+;
~H NMR (30() MHz, DMSO) 8 1.38 (s, 9H), 2.70 (t, 2H), 3.15 (q, 2H), 3.115 (s, 3H), 6.89 (t, 1 H), 7.04 (d, 1 H}, 7.37 (d, I H), 7.49 (dd, 1 H). 7.75 (dd, I H). 7.~5 (dd, 1 H), R. I I (d, 1 H), X.16 (d. 1 H), $.30 (s, 1 H), 1;.4f~ (s, 1 H), 9.07 (s, 2H), 9.42 (s, 2H) ;
Anal. calc'd for C2yH3«F3N~Oy().2S HBO: C, 61.97; H, 5.47; N, 7.411. Found: C, 61.11; H, 5.14; N, 7.21.
Example 123 I, 1-dimethvlethvl ff4-ff6-(aminoiminomethyI)-~-naphathalenyllethynvllohenyllmeth ~Lll, 3« carbamate mono(trifluoroacetate)(salt~
Example 123A
Using 4-bromobenzylamine, and the procedure described in Example 63C, the desired compound was obtained.

SUBSTITUTE SHEET (RULE 26) MS (DCI/NH3) m/z 303 (M+NH4)+.
Example 123B
Using the procedure described for Example 121A, and substituting the product obtained s in Example 123 for 4-iodoaniline, the desired compound was obtained.
MS (DCI/NH3) m/z 400 (M+NH4)+.
Example 123C
1, 1-dimethvlethvl [[4-[[6-faminoiminometh 1)-~-naphathalenyliethynyllphenyllmeth rL1) carbamate, mono(trifluoroacetate)(salt) Using the product obtained in Example 123B and the procedure described in Example 40D, the desired compound was obtained.
MS (DCl/NH3) m/z 400 (M+H)+;
1 H NMR (3()() MHz, DMSO) 8 1.40 (s, 9H), 4.1 H (d, 2H), 7.34 (d, 2H), 7.45 (t, 1 H), 7.5k (d, 2H), 7.78 (dd, 1 H), 7.H6 (dd, 1 H), H.15 (d, 1 H), 8.19 (d, I H), 8.31 (s, 1 H), H.50 (s, 1 H), 9.1()-9.42 (s, 4H) ;
Anal. calc'd for C27H2~,F3N304: C, 63.15; H, 5.10; N, K.18. Found: C, 62.95;
H, 4.97; N, H.09.
'~> Example i 24 6-[[4-(aminomethvl)phenyliethynvll-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) Trifluoroacetic acid (0.73 mL) was added dropwise to a suspension of the product obtained in Example 123C (80 mg, 0.2 mmol) and 1.5 mL CH2CI2. The reaction mixture was 'a stirred for 0.25 hour at room temperature, then was evaporated to dryness under vacuum.
Toluene was added and evaporated under vacuum several times to afford a tan solid which was purified by reverse phase chromatography, eluting with methanol / 0.1 plc aqueous TFA to afford the desired compound.
MS (APCI) m/z 300 (M+H)+;
3n iH NMR (300 MHz, DMSO) 84.10 (s, 2H), 7.55 (d, 2H), 7.70 (d, 2H), 7.79 (dd, 1H), 7.89 (dd, I H), H.16 (d, 1 H), 8.19 (d, 1 f-I), H.20 (s, 2H), 8.36 (s, 1 H), 8.53 (S, 1 H), 9.20 (s, 2H), 9.44 (s, 2H);
Anal. calc'd for C24H IyF~N304: C, 54.66; H, 3.63; N, 7.97. Found: C, 54.42;
H, 3.57; N, 7.76.
-14l-SUBSTITUTE SHEET (RULE 26) Example 125 6-f f 3-l2-aminoethvll-4-methoxyphenvIlethynyll-2-naphthalenecarboximidamide bis(trifluoroacetate)ls~lr~
S
Using the product obtained in Example 122C and the procedure described for Example 124, the desired compound was obtained.
MS (ESI) m/z 344 (M+H)+;
~H NMR (300 MHz, DMSO) 8 2.90 (t, 2H), 3.06 (t, 2H), 3.88 (s, 3H), 7.1 I (d, iH), 7.44 lu (d, 1 H), 7.~7 (dd. 1 H), 7.75 (dd, 1 H), 7.82 (s. 2H), 7.88 (dd, 1 H), 8.
I 2 (d, 1 H), 8.17 (d, 1H), 8.28 (s, IH), 8.50 (s, 1H), 9.20 (s, '?H), 9.45 (s, 2H);
Anal. calc'd for C26H23F6N~05~U.5 H20: C, 53.80; H, 4.17; N, 7.24. Found: C, 53.89; H, 4.31; N, 6.83.
> > Example 126 -II4-(hvdroxvmethvl)phen Iy~rhvnyll-2-naphthalenecarboximidamide monoltrifluoroacetate)l alt) Example 126A
2( Using the procedure described for Example 121A, and substituting 4-bromobenzyl alcohol for 4-iodoaniline, the desired compound was obtained.
MS (DCI/NH3j m/z 301 (M+NH4j+.
Example 126B
?S f~-I14-(hvdroxvmethvf )phenvl-lethyn~l I-2-naphthalenecarboximidamide mono(trifluoroacetate)lsalt) Using the product obtained in Example 126A and the procedure described in Example 94B the desired compound was obtained.
MS (ESI) m/z 3()1 (M+H)+;
3U ~ H NMR (300 MHz, DMSO) 8 4.58 (d, 2H), 5.32 (t, 1 H), 7.41 (d, 2H), 7.59 (d, 1 H), 7.79 (dd, 1 H), 7.86 (dd, 1 H), 8.12 (d, 1 H), 8.18 (d, 1 H), 8.32 (s, 1 H), 8.50 (s, 1 H), 9.14 (s, 2H), 9.46 (s, 2H);
Anal. calc'd for C22H1~F3N203~0.5 H20: C, 62.41; H, 4.29; N, 6.62. Found: C, 62.56; H, 4.13; N, 6.65.

SUBSTITUTE SHEET (RULE 26) Exam lie 127 6-f( 1. 2, 3, 4-tetrahvdro-6-isoquinolin Iv )ethynyll-2-naphthalenecarboximidamide bis(trifluoroacetate )(salt) Exams a 127A
A solution of boron tribromide ( 1.2 mL, 12.5 mmol) and 12.5 mL CH2Cl2 was added dropwise to a -78° solution of 6-methoxytetrahydroisoquinoline ( I.0 g, 5.0 mole, Org. Synth., 67. 60, 1988} and 38 mL CH2C12. The reaction mixture was stirred for 1 hour at -78°, 1 hour at 1() 0°, and 0.25 hour at room temperature. The reaction mixture was cooled to -78°, and 20 mL
methanol was added dropwise. The solution was stirred for 1 hour at room temperature.
Solvent was evaporated under vacuum and the residue was dried under vacuum to afford the desired compound.
MS (DCI} m/z 150 (M+H)+.
IS
Example 127B
The produe;t obtained in Example 127A ( 1.15 g, 5.0 mmol) was subjected to the conditions described in Example 63C. A 2.1 g portion of this material was stirred at reflux for 1.5 hour with 6() mL methanol and 9 mL l0~lo aqueous NaOH. After cooling to room 2o temperature, methanol was evaporated under vacuum. Water was added and the solution was acidified with 6 N HCI. The mixture was extracted with CH2CI2. The organic layer was washed with water, saturated aqueous sodium chloride, dried (MgS04), filtered, and solvent evaporated under vacuum to afford the desired compound.
MS (DCI/NH3) m/z 267 (M+NH4}+.

Example 1270 Using the product from Example 127B and the procedure described in Example 28B, the desired compound was obtained.
MS (DCI/NH3) m/z 399 (M+NH4)+.
3(l Example 127D
Using the procedure described for Example 121A, and substituting the produca obtained in Example I27C for 4-iodoaniline, the desired compound was obtained.
MS (DCI/NH3) m/z 426 (M+NH4)+, SUBSTITUTE SHEET (RULE 26) Example 127E
Using the product obtained in Example 127D and the procedure described in Example 40D, the desired compound was obtained.
MS (ESI) m/z 426 (M+H)+;
~ H NMR (300 MHz, DMSO) b 1.45 (s, 9H), 2.82 (t, 2H), 3.59 (t, 2H), 4.58 (s, 2H), 7.29 (d, 1 H), 7.42 (d, 2H), 7.76 (dd, 1 H), 7.83 (dd, 1 H), 8.15 (d, 1 H), 8.19 (d, 1 H), 8.35 (s, 1 H), 8.51 (s, ( 1 H), 9.20 (s, 2H), 9.45 (s, 2H).
«> Example 127F
6-f ( 1. 2. 3. 4-tetrahvdro-f~-isoquinolin~l)ethynyll-2-naphthalenecarboximidamide bis(trifluoroacetate)( alt) Using the product obtained in Example 127E and the procedure described in Example 124D, the desired compound was obtained.
n MS (ES1) m/z 326 (M+H)+;
~ H NMR (300 MI-lz, DMSO) 8 3.03 (t, 2H), 3.42 (t, 2H), 4.35 (s, 2H), 7.35 (d, 1 H), 7.46 (d, ZH), 7.78 (dd, I H), 7.89 (dd, 1 H), 8.15 (d, 1 H), 8.19 (d, I H), 8.35 (s, 1 H), 8.52 (s, 1 H), 9.17 (s, 2H), 9.31 (s, 2H), 9.48 (s, 2H);
Anal. calc'd for C2~HZIF~,N304: C, 56.42; H, 3.82; N, 7.59. Found: C, 56.31;
H, 3.81; N, 2n 7.42.
Example 129 5-flfi-(aminoiminomethvl)-2-naohthalenylloxylpentanoic acid mono(trifluoroacetate)(salt) 'S Example 129A
The resulting product from Example 3 19A (250 mg, 1.477 mmol) was treated with methyl 5-bromovalerate in an analogous manner as described in Example I 19B to yield the desired compound (394 mg, 9410).
MS (DCI (NH3)) m/z 301 (M+NH4)+.
3~
Example 129B
5-ff6-(aminoiminomethvll-2-naphthalen~rlloxyjpentanoic acid mono(trifluoroacetate)(snlt) The resulting product from Example 129A (262 mg, 0.8723 mmol) was treated in an analogous manner as described in Example 94D to yield the ester amidine product. The product SUBSTITUTE SHEET (RULE 26) ( 140 mg, 0.542 mmol} was dissolved in methanol ( 1 1 mL). To this was added a solution of lithium hydroxide (68.2 mg, 1.626 mmol) in water (3 mL) and the resulting mixture was stirred at room temperature under an inert atmosphere for 18 hours. The reaction was evaporated and the residue purified by reverse phase chromatography to yield the desired compound ( 184 mg, 74%).
MS (DCI (NH3)) m/z 287 (M+H) +;
tH NMR (300 MHz, DMSO-d6} 8 1.71 I (m, 2H}, 1.817 (m, 2H), 2.320 (t, 2H), 4.144 (t, 2H), 7.377 (dd, 1 H), 7.472 (d, 1 H), 7.632 (dd, 1 H), 7.980 (d, 1 H), 8.()81 (d. 1 H), 8.329 (s ! H), 9.100 (br s, 2H), 9.390 (br s, 2H}, 12.100 (br s, 1 H);
m Anal. calc'd for C~6H1gN203~ (C2H02F3) 1.15~H200.65: C, 51.22; H, 4.80; N, 6.53.
Found: C, 51.30; H, 5.07; N, 6.12.
Exam,~le 131 7-methoxv-1;-( 3-oxo-1-cvclopenten-1-yl )-2-naphthalenecarboximidamide t ~ mono(trifluoroacetate)(salt) Example 131 A
The material prepared as described in Example 25A (0.5 g, I.5 mmol) and the 3-tributylstannyl-2-cyclopentenone prepared as described by Labourde et al. Tet Letters 31, (13), 2( 11(37-1 H40 ( 1990) are coupled via Pd catalyst as described by the method of Stilie et al. .IACS
109, 54711-541;6 ( 1987) yielding after flash chromatography with 3: 1 hexanes/ethyl acetate a white solid. 300 mg, 72%.
MS (DCI/NH3}: 21;1 (M+NH4).
Example I 31 B
7-methoxv-H-( 3-oxo- I -i:yc l openten-1-yl )-~-naphthalenecarbox imidamide mono(trifluoroacetate)(salrl The material prepared above (130 mg, .4 mmol) is prepared according to the H2S/pyridine method described in Example 40D. The desired compound was obtained as an 30 off-white solid after reverse phase chromatography. 52 mg, 45%.
MS (DCI/NH3): M+H+ 28 I
t H NMR (DMSO-d6): 9.45 (bs, 2H); 9.12 (bs, 2H), 8.25 -8.32 (m, 2H), 8.20 (dd, 1 H), 7.86 (d, 1 H), 7.75 (dd, 1 H), 6.42 (m, 1 H), 4.05 (s, 3H), 3.15 (m, 2H), 2.75 (m, 2H) SUBSTITUTE SHEET (RUtE 26) WO 99!05096 PCTIUS98/15386 Anal. calc'd for C1yH17N204F3~1.75 TFA: C, 57.87; H, 4.35; N. 7.10. Found: C, 51.37; H, 4.21; N, 7.14.
Example 132 ~aminoiminomethyl)-N-(4-methylphenyl)-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) Example 132A
p-Toluidine (0.11 g, 1 mmol), and the cyano ester prepared in Example 8E (0.2 g, 1 m mmol) are coupled according to the procedure described in Example RG, providing an off-white solid as the desired compound (0.16 g, 56%).
MS (ESl +, -): 287 (M+) ; 285 (M-).
Example 132 B
t s 6-(aminoiminomethyl)-N-(4-methxlphenyl )-2-n~hthalenecarboxamide mono(trifluoroacetate)(salt~
The desired compound is prepared according to the procedure described in Example 6B
and purified as described in Example 1 B, yielding a white solid (35 mg, 35%).
MS (ESI +): 304 (M+) 2s~ I HNMR (DMSO-d6j: 10.55 (s, 1 H); 9.45 (bs, 2H); 9.15 (bs, 2H); 8.65 (s, 1 H); 8.58 (s, I H);
R.32 (d, I H), 8.20 (d, 1 H), 8.19 (dd, 1 H); 7.9h (dd, 1 Hj, 7.75 (d, 2H), 7.12 (d, 2H), 2.35 (s, 3Hj;
Anal. calc'd for C2)H1~N3O~F3: C, 60.43; H, 4.35; N, 1().07 Found: C, 59.94;
H, 4.Ofi; N, 9. R(1.
,5 Example 133 methyl 4-1 f 17-(aminoiminomethyi )-1-(~-pvrimidinylamino )-2-naphthalenyl foxy !methyl 1 benzoate, mono(trifluoroacetate)(salt) ~t> Example 133A
The material described in Example 91 A is treated with All3 according to the procedure described in Example I I9A and alkylated with 4-CarbomethoxyBenzylbromide according to the procedure described in Example 109B, yielding the desired compound as a white solid, 100 mg, 8370.

SUBSTITUTE SHEET (RULE 26) MS (ESI +, -): 41 I (M+) ; 409 (M-) Example 1338 methyl 4-lff7-(aminoiminomethyl)-1-(2-pyrimidinylamino)-2-naphthalen lv loxylmet~ll benzoate, mono(trifluoroacetate)(salt) The desired compound is prepared according to the procedure described in Example 40D and purified according to the procedure described in Example 1 19B, yielding a light yellow solid, (49 mg, 5()~0).
MS (ESI +, -): 42R (M+); 426 (M-) lu I H NMR (DMSO-d6): 9.45 (bs, 2H); 9. I S (s, 1 H); 8.97 (bs. 2H); 8.45 (dd.
I H); 8.38 (d, 1 H); 8.15 (d, I H ), 8.09 (d, I H), 7.95 (d, 2H); 7.76 (d, 1 H), 7.68 (dd, 1 H), 7.35 (d, 2H), 6.85 (d, 2H), 5.39 (s, 2H); 3.85 (s, 3H);
Anal. calc'd for C2~H22N505F~: C, 57.67; H, 4.10; N, 12.93 Found: C, 55.34: H, 3.88; N, I 2.05.
IS
Exam lp a 134 4-1117-(aminoiminomethvll-1-(2-p rimidin_~rlamino)-2-naphthalenylloxyjmethyl~
benzoic acid, mono(trifluoroacetate)(saltl 20 The material prepared in Example 134 (40 mg) is dissolved in 1: 1 THF/water. To the clear solution is added LiOH~water (9 mg), the resulting clear solution is stirred 18 hours at room temperature. The reaction mixture is concentrated to a yellow solid. The solid is dissolved in distilled water. acidified to pH 2 with 3 N HCI and stirred 2 hours at room temperature. The desired compound is isolated by filtration, dried under vacuum as a yellow solid. Yield: 39 mg 25 (46~%) MS (APCI): M+H+: 414 ( H NMR (DMSO-dfi): 9.45 (bs, 2H); 9.15 (s, I H); 8.97 (bs, 2H); 8.45 (dd, 1 H); 8.38 (d, 1 H); 8. I S (d, 1 H ), 8.09 (d, 1 H), 7.95 (d, 2H); 7.76 (d, 1 H}, 7.68 (dd.
1 H), 7.35 (d, 2H), 6.85 (d, ZH), 5.39 (s, 2H);
3u Anal. calc'd for C25HZ~~N505F3C1~3 H20: C, 48.67; H, 4.25; N, I 1.35 Found:
C, 49.64; H, 4.44; N, 11.69.
Example 135 SUBSTITUTE SHEET (RULE 26) WO 99105096 PCTlUS98115386 I, 1-dimethvlethyl ff4-f((6-laminoiminomethyl)-2-naphathalenyllaminolcarbonyll phen ll~yllcarbamate, monoltrif(uoroacetate)lsalt) Example 135A
The material prepared in Example 8B was added to cold (0°C) sulfuric acid (45 mL).
Within I minutes at 0°C bubling started to form. Allowed to bubble at 0°C for 30 minutes than slowly warmed to room temperature. Left at room temperature for 20 minutes.
then poured into ice and diluted with water (to approx. 500 mL). The suspension was placed in an ice bath and carefully added a solution of 50% aqueuos sodium hydroxide so that the temperature would not I~r exceed 35°C. The light yellow solid was filtered than washed with water till the wash became neutral to pH paper (7.0). The product was dried under vacuum. The product was purified on silica gel column using 20°lo ethyl acetate 80% hexanes as eluent to yield 3.3 g (67%) of light yellow solid.
MS m/z ! f~9 (M+1 )+.
IS
Example 135B
A solution of Example 135A (135 mg, 0.8 mmol), 4-N-Boc-aminomethylbenzoic acid (404 mg, l .6 mmol) and EDCI (307 mg, 1.6 mmol) in methylene chloride (25 mL), at room temperature, was added DMAP (3 mg) and stirred overnight. The reaction mixture was diluted 2o with methylene chloride (60 mL) then washed 2% aqueous hydrochloric acid (2x30 mL), water (20 mL), 0.5 M aqeuos sodium hydroxide (2x50 mL) and brine. The organic phase was dried over magnesium sulfate and evapoorated. The product was purified via on silica column usinga gradient of 25% to 60% ethyl acetate in hexanes as eluent. Yield 175 mg (54%) of white powder.
~S
Example 135C
1, I-dimethvlethvl lf4-(ff6-laminoiminomethyl)-~-naphathalenyllarninolcarbonvll ohenyllmethvllcarbamate, mono(trifluoroacetate)lsalt) The reaction was carried out in the same manner as described in Example 40D.
Yield 3() 1 10 mg (64%).
MS m/z 40R (M+( )+' 425 (M+l li)+
I H NMR: 3.30 (s, 9H), 4.22 (d, 2H, J=7.1 Hz), 7.42 (d, 2H, J=8.5Hz), 7.49 (t, 1 H, J=7. I Hz), 7.79 (dd, 1 H, J 1=8.2Hz, J2=2.0Hz), 7.95-8.00 (m, 3H), 8.09 (d, 2H, J=H.4Hz), $.42 (s> 1H), (i.63 (d, 1H, J=2.OHz), 9.lii (br s, 4H), 10.58 (s, 1H);

SUBSTITUTE SHEET (RULE 26) Anal. c:alc'd for C~~,H2~F3N405: C, 58.55; H, 4.85; N, 10.41. Found: C, 58.64;
H, 5.11; N, 10.52.
Exam 1 S N-f6-laminoiminomethyl)-2-naphthalenyl)benzamide monoltrifluoroacetate)(salt) The desired compound is prepared as described in Example 135;
tH NMR (300 MHz, DMSO-d~,j 10.67 (s, IH), 9.25 (br.s, 4H), $.65 (d, J=I.SHz, 1H), 8.43 (d, J=l.4Hz, 1H), 8.10 (d, J=9.2Hz, 2H), 8.03-7.97 (m, 3H), 7.81-7.78 (m, 1H), 7.65-7.55 m (m, 3H).
MS (ESI/NH3) m/z 290 (M+H)+;
Anal. calc'd for C~gH~5N30~CF3COOH: C, 59.55; H, 4.00; F, 14.13; N, 10.42.
Found: C, 50.47; H, 3.88; F, 14.42; N, 10.39.
s Example 137 1, 1-dimethvlethvl ff4-lff6-laminoiminomet~l)-2-naphathalenvllaminolcarbonyll cvclohexvlllmethvllcarbamate mono(trifluoroacetate)lsaltl Example 137A
2e To a solution of the 6-Amino-2-naphthalenecarbonitrile prepared in Example 73 ( 100 mg, 0.6 mmol) in methylene chloride (35 mL) at room temperature, was added I-carboxy-4-(Boc-aminomethyl)cyclohexanes (2R0 mg, 1.1 mmol) followed by 1-ethyl-3- (3-dimethylaminopropyt)carbodiimide hydrochloride (EDAC, 225 mg, 1.2 mmol). After 5 minutes to the reaction mixture was added DMAP (20 mg, c:atalytic:). The reaction was stirred at room ?~ temperature for 72 hours. The reaction mixture was diluted 7: 3 ethyl acetate: hexanes then filtered through silica gel and washed with the name solvent mixture.
The organic solvent was washed by aq. Acid (2% Hcl, 2x50 mL), water and aq.
Base ( 10C/e NaOH, SO mL). The solvent was dried over magnesium sulfate filtered and evaporated.
Crystalization from ether/ hexanes afforded the product as white solid. Yield 166 mg (68%).
3n MS (DCI/NH3) m/z 40); (M+H)'~.
Example 1 ~7B
l, 1-dimethvlethv) ff4-fff6-(aminoiminometh 1)-2-naphathalenvIjaminolcarbonvll cvclohexv(llmethvllcarbamate monoltrifluoroacetate~(salt) SUBSTITUTE SHEET (RULE 26) A solution of the substrate (Example 137A) in Pyr: Et3N ( 1(?: 1, 20 mL) was bubbled HZS for 5 minutes. Stirred at room temperature overnight. The reaction mixture was added ethyl acetate ( 100 mL) followed by 1 % aq. KHS04 (60 mL) and separated:
washed organic layer with water (2x50 mL), sodium bicarb. And brine, dried over magnesium sulfate &
S evaporated. To a suspension of the resulting solid in acetone (25 mL) and added MeI (1.0 mL).
Stirred at 50°C for 2 hours, all dissolved. Evaporated solvent to a complete dryness and added methanol (30 mL) and ammonium acetate ( 150 mg}. The mixture was stirred at room temperature overnight. Purification by Reverse Phase Cig MPLC. After evaporation added toluene & evaporated (2x40 mL). The resulting oil was treated with methanol and ether and the U product precipitated as white solid (72 mg, 43%).
MS (ESI/NH3) m/z 425 (M+H)+;
~H NMR (300 MHz, DMSO-d~,) 1().24 (s, IH), 9.05 (br.s, 4H), 8.49 (s, IH), 8.38 (d, J=l.7Hz, 1 H), 8.03-8.00 (m, 2H), 7.77-7.74 (m, 2H), 6.93-6.91 (m, I H), 2.83-2.79 (m, 2H), 2.4t)-2.30 (ml), 1.92-1.75 (m, 4H), 1.50-1.45 (m, 1H), 1.39 (s, 9H), 0.96-0.91 (m, S 4H);
Anal. valc'd for Cz4H;;~N.~03~CF3COOH: C, 57.98; H, 6.18; N, 1().40. Found: C, 57.63; H, 6.24; N, 10.21.
Example 138 20 N-16-(aminoiminomethvl)-?-naphthalenyll-N'-f4-aminopheny~urea bis(trifluoroacetate)(salt) Example 138A
To a solution of the compound prepared in Example 40B (194.2 mg, 1 mmol) in dioxane ( 1 () mL) at room temperature, was added 4-phenylenediamine mono Boc (416, 5 mg, 2 25 mmol). The product started to precipitate within minutes. After an hour the reaction mixture was added ether (5 mL) and the white solid product was filtered and washed with ether to yield 350 mg (87C/c).
MS (DCI/NH~) m/z 403 (M+H)+.
> Exam_ple 138B
A solution of the corresponding nitrile prepared in Example 138A (105 mg, 0.36 mmolj in Pyr: Et3N ( 10: 1, 20 mL) was bubbled H2S for 5 minutes and stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate ( 100 mL) washed with aqueous 0.25 N HCl (25 mL) followed by water (2x50 mLj, saturated solution of sodium bicarbonate, SUBSTITUTE SHEET (RULE 26) and brine, dried over magnesium sulfate & evaporated. To a solution of the resulting solid in acetone (25 rnL) was added MeI ( 1.() mL)and stirred at 50°C for 30 minutes- very strong precipitate was observed. Added ether and filtered the yellow precipitated.
The yellow solid was added methanol ( 10 mL} and ammonium acetate ( 150 mg) and stirred at room temperature S overnight. Purified as described inExample 1B. Yield of the white solid 69 mg.
MS (DCIINH3) m/z 420 (M+H)+.
Example I38C
N-16-laminoiminomethvl)-2-naphthalenyll-N'-(4-aminophenyl)urea bisltrifluoroacetate)(salt) lU The Boc protected substrate (Example 138B) was dissolved in methylene chloride: T'FA
1: 1 (25 mL) and stirred at room temperature forl hour. Evaporated solvent under vacuum added toluene & evaporated again. Added water & little acetonitrile, filtered & lyophilized. 36 mg of white solid.
MS (ESI/NH3) m/z 32() (M+H)+;
l5 ~ 1-1 NMR (300 MHz, DMSO-d~,} 9.26 (br.s, 2H), 9.2 I (br.s, 1 H), 8.85 (br.s, 2H), 8.31 (d, J=l.7Hz. 1H), 8.18 (d, J=l.7Hz, IH}, 7.95-7.91 (m, 2H), 7.68 (dd, J1=fi.6Hz, J2=2.0Hz, 1 H), 7.57 (dd, J I=9.2Hz, J2=l.4Hz, 1 H), 7.34 (d, J=8.8Hz, 21-i), 6.91 (d, J=8.4Hz, 2H};
Anal. catc'd for C~gHI~N50~2~CF3COOH~H20: C, 46.73: H, 3.74; N, 12.39. Found:
C, C, 47.03: H, 3.55: N, 12.36.

Example 139 N-16-laminoiminomethvl)-2-naphthalenvll-4-4-laminometh~ c~exanescarboxamide bisltrifluoroacetate)(salt,}
25 A solution of the substrate prepared in Example 137 as TFA salt (45 mg) in methylene chloride: TFA 1: 1 (20 mL) was stirred at room temperature for 1 hour. The solvent was evaporated under vacuum, added toluene & evaporated (20 mLx2). Dissolved in water, filtered-0.45~ frit and lyophilized. 35 mg, white solid as bis TFA salt.
MS (ESI/NH~) m/z 325 (M+H)+;
30 ~H NMR (300 MHz, DMSO-d~,) 10.31 (s, 1H), 9.31 (br.s, 2H), 9.10 (br.s, 2H}, 8.49 (s, IH), 8.39 (s, 1H), 8.04-8.00 (m, 2H), 7.78-7.71 (m, 2H), 2.71 (d, J=7.OHz, 2H), 2.44-2.36 (m, 1H)1.96-1.85 (m, 4H), 1.61-1.42 (m, 3H), 1.()9-1.02 (m, 2H);
Anal. calc'd for C~yH~4N40~2~CF3COOH: C, 50.00; H, 4.74; N, 10.14. Found: C, 49.95;
H, 4.70; N, 09.96.

SU8ST1TUTE SHEET (RULE 26) Exam l N-f6-(aminoiminometh ly )-2-naphthalenvll-i'd'-f(4-aminomethyl) henyl urea bis(trifluoroacetate)(salt~
s Ex~m~le 140A
To a solution of the isocyanate prepared in Example 40B ( 140 mg, 0.72 mmol) in dioxane (8.0 mL) at room temperature, was added 4-N-Boc-aminomethylbenzoic acid (320 mg, 1.44 mmol) and stirred for I hour. The product was precipitating during the reaction. The W mixture diluted with ether (15 mL), filtered and washed with ether to yield 215 mg {72%) of white solid.
MS (DCI/NH3) m/z 417 (M+H)+.
Example 140B
n A solution of the nitrile (Example 14()A) ( 198 mg, (1.47 mmol) in 10: 1 pyridine:
triethylamine ( 10 ml.,) was treated with H2S for 5 min, stirred at room temperature for I S h and concentrated. The resulting solid was dissolved in acetone (15 mLj, treated with iodomethane (0.1i mL, 12.H mmol), stirred for 2 hours, diluted with ether ( 10 mL), filtered, washed with ether and dried under vacuum. The resulting solid was dissolved in methanol (4 mL) and was ?U added NH40Ac (200 mg, 2.6 mmol) at room temperature overnight. The product was purified according to the procedure described in Example IB to provide 112 mg (54%) of the corresponding amidine.
MS (DCI/NH3) m/z 434 (M+H)+.
Example 140C
N-ffi-(aminoiminomethyl)-~-naphthalenyll-N'-f (4-aminomethyl)~henyl lurea bis(trifluoroacetate)(salt) A solution of the substrate (Example 140B) in methylene chloride: TFA 1: 1 (20 mL) was stirred at room temperature for 1 hour. The solvent was evaporated under vacuum, added 3t) toluene & evaporated (20 mLx2). Dissolved in water, filtered- 0.45, frit and lyophilized. 38.1 mg, white solid.
MS (ESi/NH3) m/z 334 (M+H}+;
t H NMR (300 MHz, DMSO-d6} 9.68 (s, 1 H), 9.45 (s, 1 H), 9.35 (br.s, 2H), 9.08 (br. s, 2H), 8.40 (d, J=l.7Hz, 1H), 8.31 (d, J=l.BHz, 1H), 8.10 (br.s, 3H), 8.04-7.99 (m, 2H), SUBSTITUTE SHEET (RULE 26) 7.76 (dd, Jl=8.8Hz, J2=l.BHz, 1H), 7.67 (dd, J1=8.8Hz, J2=l.7Hz, IH), 7.58 (d, J=8.4Hz, 2H), 7.39 (d, J=8.4Hz, 2H), 3.98 (br. s, 2H);
Anal. calc'd for ClyH~gN5012~CF3COOH~H20: C, 47.67; H, 4.00; F, 19.67; N, 12.09.
Found: C, 47.33; H, 3.70; F, 19.59; N, 11.71.
Example 141 methvl 17-(aminoiminomethvil-3-f f f4-laminometh~lDhenyllaminolcarbonyl~ l ~,vhathalenvllcarbamate bis(trifluoroacetate)(salt) Example l 41 A
To a solution of the ester, prepared as described in Example 26, (747 mg, 2.63 mmol) in dioxane ( 10 mL) was added acetone ( 1 mL) and an excess of sodium hydroxide ( I N in water, 10 mL). After 1 hour the mixture was added water (40 mL) and ethyl acetate (85 mL) then was acidified with lU~7c aq. HCI. The ethyl acetate layer was separa~ed washed with water (2x2() mL) then brine, dried over magnesium sulfate filtered and evaporated.
The product was isolated as a light yellow solid.
MS m/z 271 (M+1 )t.
Example 141 B
To a suspension of naphthoic acid derivative, prepared in Example 141 A (270 mg, I .1 mmol) in methylene chloride (8.0 mL) was added diisopropylethylamine (DIEA, 485~.L, 2.8 mmol) followed by O- (azabenzotriazole-I-yl)-N, N, N', N'-tetramethyluroniumhexafiuorophosphate (HATU, 527 mg, 1.39 mmol). After 10 minutes added the 4-N-Boc-aminomethylaniline (370 mg, 1.7 mmol). After an hour, added ethyl acetate ~s ( 120 mL) and washed organic: layer with 5~/c aq. citric acid (50 mL), water (2x4() mL) and brine (50 mL). The rxn was dried over magnesium sulfate filtered through small amount of silica and evaporated. Purification on silica eluting with ethyl acetate in hexanes. The product, after concentration, was added ethyl acetate and ether and filtered to yield 350.0 mg (7010) of yellow solid.
MS m/z 447 (M+I )+.
Example 141 C
A suspension of the naph derivative (Example 141B) (300 mg, 0.67 mmol) in ethyl acetate (20 mL) was added 120 mg of the Pd catalysit then stirred at room temperature, under SUBSTITUTE SHEET (RULE 26) hydrogen, at atmospheric pressure and stirred for I hour.. The crude was carried on to the next step without any purifications or analysis.
To a solution of the crude amine in dioxane {25 mL) and 10% aqeuos sodium carbonate (2.5 mL) was added the methyl chlorofotmate { I .0 rnL, large excess). After 2 hours the rxn S was quenched with methanol then diluted with ethyl acetate (80 mL) and water (50 mL). The ethyl acetate Iayer was separated, dried over magnesium sulfate filtered and evaporated. The product was separated on silica column using a gradient of ethyl acetate in hexanes (from 5 to 30% ethyl acetate in hexanes). Yield 140 mg of off white solid.
MS m/z 492 (M+18)+' Example 141 D
The desired compound was prepared as described in Example 26.
M S m/z 492 (M+ 1 +.
Example 141 E
methvl f7-(aminoiminomethvl)-~-f114-(aminomethyl~phe~llaminolcarbonyll-1 naphathalenvllcarbamate bis(trifluoroacetate)(calt) A solution of the substrate (Example 141 D) in a mixture of methylene chloride: TFA 4:
1 (20 rnL) was stirred at room temperature for 15 minutes. The solvent was concentrated under 2c) vacuum, and separated on RP C 18 MPLC. Yield, 21 mg off white solid.
MS m/z 392 (M+18')+
~ H NMR (DMSO): 3.783 (s, 3H), 4.03 (q, 2H, J=S.SHz), 7.47 (d, 2H, j=8.4Hz), 7.85 (d, 2H, j=8.4Hz), 7.94 (d, 1 H, j=8.8Hz), 8.15 (wide s, 2H), 8.31 (d, 1 H, j=8.8Hz), 8.33 (s, 1 H). R.47 (s, I H). H.74 (s, 1 H), 9.29 (s, 2H), 9.47 (s, 2H), 9.90 (s, I H), 10.68 (s, 11-i).
~s Anal. calc'd for C25H25F~,N5O~ (base molecule + 2 TFA+1 H20): C. 47.04; H, 3.70; N, 10.52. Found: C, 47.1(): H, 3.95; N, 10.99.
Example 142 fi-(aminoiminomethvl)-N-(4-ethvlphenyl)-~-na~hthalenecarboramide acetate(salt) 3« Example 142A
The reaction was carried out in the same manner as described in Example 141 B.
Yield 374 mg (61 %) of white powder.
MS DCI/NH3): m/z 301 (M+NH4+).

SUBSTITUTE SHEET (RULE 26) Example 142B
6-(aminoiminomethvl)-N-(4-eth~~henyl)-2-naphthalenecarboxamide acetatelsalt) The reaction was earned out in the same manner as described for the naphthyl analog prepared in Example 141 D, 313 mg. The solid that precipitated during the last step was filtered s and washed in ether to yield 71 mg ( 18%) of white solid, as acetate salt.
MS (ECI) m/z 301 (M+H)+;
~H NMR (300 MHz, DMSO-d6) 8 1.19 (t, J=7.4Hz, 3H), 2.60 (q, J=7.4Hz, 2H), 7.22 (d, J=8.5Hz, 2H}, 7.72 (d, J=B.SHz, 2H), 7.94 (dd, JI=8.8Hz, JZ=l.7Hz, 1H), 8.08-8.23 (m, 3H), 8.47 (d, J=I .7Hz, 1 H), 8.63 (s, 1 H), 10.43 (br. s, 1 H);
lU Anal. calc'd for C2~~H19N30~AcOH~ 0.5 H20: C, 68.38; H, 6.26; N, 10.87.
Found: C, 611.56; H, 6.21; N, 10.67.
Example 143 fi~aminoiminomethyl)-N-(2-naphthalenyl)-2-n~hthalenecarboxamide monoltrifluoroacetate)(salt) Example 143A
To a solution of the acid chloride prepared as described in Example KB (341 mg, 1.6 mmol) in methylene chloride (20 mL) was added a solution of the '?-Amino naphthalene (249 2O mg, 1.74 mmol) in methylene chloride ( 10 mL) and propylene oxide ( 12 mL).
The rxn was stirred at room temperature overnight. The reaction mixture was added ether and the product was filtered, washed with ether and hexanes and dried under vacuum. Yield 440 mg (86°~0).
MS (DCI/NH3) m/z 340 (M+NH4)+.
'-5 Example 143B
6-(aminoiminomethyl)-N-(2-naphthafenyl)-2-naphthalenecarboramide mono(trifluoroacetate)(sal~
The desired compound is prepared as described in Example 141 B. Yield of white solid 40 mg ( 10°l0).
30 MS (ESI) m/z 340 (M+H)+;
1H NMR (300 MHz, DMSO-d~) 7.43-7.55 (m, 2H), 7.86-7.96 (m, 5H), 8.20-8.28 (m, 2H), H.()X-8.23 (m, 3H}, H.34 (d, J=8.8Hz, IH), H.50 (d, J=l.7Hz, IH}, 8.57 (d, J=l.3Hz, 1H), X.75 (s, 1 H}, 9.33 (br. s, 4H) 10.75 (s, I H);

SUBSTtTUTE SHEET (RULE 26) Anal. calc'd for C22H»N30~TFA~ 0.25 H20: C, 62.95: H, 4.07; N, 9.18. Found: C, 63.09;
H, 3.72; N, 8.99.
Example 144 S 6-l5-nheny!-2-oxazolvl)-2-naphthalenecarboximidamide mono(triftuoroacetate)(salt) Example 144A
To a suspension of the phenacyl amine hydrochloride (Aldrich) (415 mg, 2.42 mmol) in a mixrure of methylene chloride (50 mL) and propylene oxide ( I 5 mL) at room temperature was to added a solution of the 2-nitrite-6-acidchloride (56() mg, 2.6 mmolj in methylene chloride (30 mL) followed by DMF {3.0 mL). Thje reaction was stirred at room temperature overnight. The reaction mixture was added ether ( i 5 mL) and the product was filtered and washed with hexanes to yield 555 mg (73~1c) of white solid.
MS (DCI/NH3) m/z 3I5 (M+H)+.

Examt3le 144B
A suspension of the substrate (Example 144A) (354 mg, 1.12 mmol) in phosphorous oxychloride (3.5 mL) was boiled for 1.5 hours. The reaction mixture was poured into ice and the mixture was added ethyl acetate (80 mL) and aqeuous solution of 10%
potassium carbonate 2e) ( l00 rnL). The organic layer was separated, washed with brine dried over magnesium sulfate and evaporated. Added ether and filtered 249 mg (75%).
MS (DCL/NH3) tn/z 297 (M+H)+.
Examvle 144C
25 fi-(5-yhenvl-2-oxazolvl)-2-naphthalenecarboximidamide mono(trifluoroacetate)(salt~
To a solution of the substrate Example 1448 ( 132 mg, 0.44 mmol) in THF (20 mL) at room temperature was added a solution of 1 N LiHMDS in hexanes ( 1.5 mL, 1.5 mmol j and stirred overnight. Quenched with 4 N HCl in dioxane ( 1 mL). After 10 minutes added a few drops of water and stirred for additional 30 minutes. The solvent was evaporated under vacuum 3p and the residue was purified on reverse phase chromatography. Yield 58 mg of white solid 41 %).
MS (ESI/NH3) m/z 314 (M+H)+;
IH NMR (300 MHz, DMSO-d~) 9.50 (s, 2Hj, 9.19 (s, 2H), 8.86 (s, IH), 8.55 (s, 1H), 8.38-8.26 (m, 3H), 7.98 (s, 1H), 7.96-7.89 (m, 3H), 7.58-7.54 (m, 2H), 7.47-7.42 (m, 1H);

SUBSTITUTE SHEET (RULE 26) Anal. calc'd for C2~~H15N30~ 1.15CF3COOH: C, 60.26: H, 3.66: N, 9.45: F, 14.75. Found:
C, 60.1 I ; H, 3.H 1: N, 9.20; F, 14.81.
Exam lp a 145 s 6-(5-phenyl-2-thiazolyl)-2-naphthalenecarboximidamide mono(trifluoroacetate)(salt) Example 145A
A suspension of the substrate, prepared in Example 144A, (340 mg, 1.1 mmol) and Lawesson's reagent (60U mg, 1.48 mmol) was heated to R5°C for 4Shours.
Solvent was m evaporated to dryness and the product was isolated via silica column using 10070 ethyl acetate in hexanes as eluent. Yield: 200.0 mg (59%) of yellow solid.
MS (DC1/NH3) m/z 313 (M+H)+.
Exa ale 145B
t5 6-(5-phenyl-2-thiazolvl)-2-naphthalenecarboximidamide mono(trifluoroacetatel(salt) To a solution of the substrate, Example I45A (! HO mg, O.SH mmol) in THF (20 mL) at room temperature was added a solution of 1 N LiHMDS in hexanes (2.0 mL, 2.0 mmol) and stirred overnight. Quenched with 4 N HCl in dioxane ( 1 mL). After 10 minutes added a few 20 drops of water and stirred for additional 30 minutes. The solvent was evaporated under vacuum and the residue was purified on MPLC RPC18. Yield 36 mg (19%) of white solid.
MS (ESI/NH~) m/z 330 (M+H)+;
~ H NMR (300 MHz, DMSO-d~,j 9.49 (s, 2H), 9.14 (s, 2H), X.71 (s, 1 H), k.52 (s, 1 H), 8.47 (s, 1H), x.35-H.22 (m, 3H), 7.90-7.7H (m, 3H), 7.55-7.50 (m, 2H), 7.46-7.43 (m, IH);
'_, Anal. calc'd for C2«H15N3S~CF3COOH~H~O: C, 57.26; H, 3.93; N, 9.11. Found:
C, 56.H3;
H, 3.55; N, X.79.
Example 146 6-(aminoiminomethyl)-4-(3-furanyl)-N-(2-pyridinyl)-~-naphthalenecarboxamide 3t) dihydrochIoride Example I46A
The above product was prepared in the manner of Example 1 14A.
MS (ESI) m/z (M+H)+ 340.

SUBSTITUTE SHEET (RULE 26) Example 1468 6-(aminoiminometh ly )-4-f3-furanyi -L(2-p~linvl)-2-naphthalenecarboxamide dihvdrochloride The above was prepared from Example 146A using method described in 1458.
MS (CI) m/z (M+H)+ 357;
I H-NMR (3UU MHz, DMSO-d6) 8 I 1.27 (s, I H), 9.56 (s, 2H), 9.17 (s, 2H), 8.76 (s, I H), 8.63 (s, 1 H), 8.45-8.24 (m, SH}, 7.96-7.89 (m, 3H), 7.25 (m, 2H), 7.18 (s, 1 H):
Anal. calc'd for CZ I H ~ gN402C12 19/ 10 HCI: C, 54.33 H, 4.75 N, 12.()7.
Found: C, 54.89;
1 H, 5.28; N, 9.81.
Exam 11~ a 147 6-(aminoiminomethvl)-N-( 1. 2. 3_ 4-tetrahydro-6-c~uinolinyl)-2-n~hthalenecarboxamide~
bis(triff uoroacetate~salt}
IS
Examlale I47A
The reaction was carried out in exactly the same manner as described for Example I l8A
using 6-aminoquinoline to yield the product in 72~~c. Mass spectrum (CI+) 324 (M+I )+.
21~ Example 1478 The reaction was carried out in exactly the same manner as described for Example 1188 to yield the product in 45~% (off white solid). Mass spectrum (ESI+) 341 (M+I}+.
Example 147C
Z, 6-(aminoiminomethvl)-N-( 1. ?, 3, 4-tetrahydro-f~-duinolin~)-~-naphthalenecarboYamide bis(trifluoroacetate)(salt) To a Suspension of the substrate, Example 1478 (261 mg, U.6 mmol) in degassed methanol ( 15 mL) was added platinum oxide (IO mg, cat.). The reaction mixture was charged with hydrogen at atmospheric pressure and stirred vigorously overnight. The next day the 3e) solution was filtered through celite to remove the catalyst, and the product was purified over rnplc with RPC I 8 silica using methanol (+ (). I ~/o TFA) and water (+ 0. I
ale TFA) as eluent.
Yield 122 mg of white solid and bis TFA salt.
MS (ESI+) 345 (M+I)+;

SUBSTITUTE SHEET (RULE 26) IH NMR (DMSO-d6) 10.51 (s, 1H), 9.65 (s, 2H), 9.50 (s, ?H), 8.64 (s, IH), 8.52 (s, 1H), 8.22 (d. J=B.OHz, 1 H), 8.12 (Abq, J=9.OHz, 2H), 7.86 (d, J=9.0Hz, 1 H), 7.61 (s, I H), 7.56 (d, J=8.0Hz, 1H), 6.98 (d, J=B.SHz, IH), 3.28 (t, J=S.SHz. 2H), 2.75 (t, J=6.3Hz, 2H), I .92-1.86 (m, 2H);
S Anal. calc'd for C21H20N40+2.25 TFA+().25 H20: C, 50.59 (50.46); H, 3.79 (3.79); N, 9.25 (9.25); F, 21.18 (20.83).
Example 148 7-methoxy-8-(pyrazinyloxy)-2-naphthalenecarboximidamide dimethanesuIfonate(salt) Example 148A
The product from Example 4A ( 125 mg, 0.627 mmol) was combined with chloropyrazine ( 1 12 mL, I.25 mmol) and Cs2C03 (409 mg, 1.25 mmol) in N-methylpyrrolidinone (4 mL), and the reaction was stirred at 130 °C for 1 hour. The reaction was I5 pooled, and the crude mixture was chromatographed on Si0? using 409e ethyl acetate/hexanes as eluent, to yield 75 mg (43%) of the desired compound.
MS (DCI (NHS) m/z 2711 (M+H)+.
Example 148B
2U 7-methoxv-8-(pvrazinvloxv)-2-naphthalenecarboximidamide dimethanesulfonate(salt) The product from Example 148A (70 mg, 0.252 mmol) was subjected to the procedure described in Example 1B to yield the desired compound (106 mg, 71~7c). m.p.
155° C.
MS (DCI (NH3) m/z 295 (M+H)+;
~H NMR (300 MHz, DMSO) b 9.42 (br s, 2H), 9.()4 (br s, 2H), 8.72 (s, 1H), 8.38 (d, J=3 ?s Hz, 1 H), 8.36 (m. 1 H), 8.21 (d. J=9 Hz, 1 H ), 8.09 (m, 1 H). 8.06 (d, J=9 Hz, 1 H), 7.82 (d>
J=9 Hz, I f-I), 7.73 (dd, J=9, 2 Hz, 1 H), 3.83 (s, 3H), 2.38 (s, 3H);
Anal. calc'd for C~~H22N4S20~' 1.1 CH4S03: C, 38.74; H, 4.49; N, 9.46. Found:
C, 38.68;
H, 4.53; N, 9.34.
3o Example 149 7-methoxv-H-(phenylthio)-2-naphthalenecarboximidamide methanesulfonate Example 149A

SUBSTITUTE SHEET (RULE 26) To a solution of NaH (48 mg, 60%, 1.2 mmol) in HMPA (2 mLj was added PhSH
(0.133 mL, 1.3 mmol), and the reaction was stirred for 5 minutes. To this was added the product from Example 53B (309 mg, 1 mmol), and the reaction was heated at 100°C for 3 hours. The crude reaction mixture was chromatographed on Si02 using 20% ethyl acetate/hexanes as eluent. The product was taken up in ethyl acetate { 10 mL) and methanol ( 10 mL), and treated with a 2 M solution of TMSCHN2 (10 mL). The reaction was stirred for 60 minutes and condensed. The crude product was chromatographed on Si02 using 15%
ethyl acetate/hexanes as eluent, to yield 1 I5 mg (39%) of the desired compound:
MS {DCI (NH3) m/z 309 (M+NH4)+.
»3 Example 149B
7-methoxv-8-(nhenvlthio)-2-naphthalenecarboximidamide rnethanesulfonate The desired compound was prepared from Example 149A and the procedure of Example SSD.
l5 MS (DCl/NH3) rn/z 309 (M+H)+;
~ H NMR (300 MHz, DMSO-d~,) 8 2.33 (s, 3H), 3.96 (s, 3H), 6.96 (d, 2H), 7.1 1 (dd, I H), 7.20 (d, l H), 7.22 (d, 1 H), 7.69 (dd, 1 H), 7.112 (d, 1 H ), 8.22 (d. 1 H), 8.33 (d, 1 H), 8.81 (s, 1 H), 9.() I (br s, 2H), 9.46 (br s, 2H);
Anal. calc'd for C«HI~,N~OS~1.15 CH4S03: C, 54.91; H, 4.96; N, 6.69. Found: C, 54.70;
2c> H, 5.15; N, 6.58.
Example 150 7-methoxv-~-(nvrazinvlamino)-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) ''S The desired compound was prepared from the product prepared in Example 90D
using the method described in Example 91 A, then converted to the amidine as described in Example 40D.
MS (DCI/NH3) m/z (M+H)+ 294;
~ H-NMR (300 MHz, DMSO-d~,) 8 9.39 (s, 2H), 9.02 (s, 2H), 8.95 (s, 1 H), 8.40 (d, 1 H), 30 8.14 (d, 1 H), 8.03 (s, 2H), 7.92 (dd, I H), 7.84 (d, I H), 7.76 (d, 1 H) 7.66 (dd 1 H), 3.90 (s, 3H);
Anal. calc'd for C~pHi~N505Fr; I/2 TFA: C, 43.79; H, 3.07; N, 12.20. Found: C;
43.81; H, 3.22; N, 12.24.

SUBSTtTUTE SHEET (RULE 26) Example 152 6-(aminoiminomethvl)-4-(3-furanvl)-N-phen 1-2-nanhthalenecarboxamide monohydrochloride Examlale 152A
To a solution of the product from Example 8D (5.50 g, 26.04 mmol) in CH2CI2 {

mL) was added dibromodimethylhydantoin (4.47 g, 15.62 mmol) and trifluoromethanesulfonic acid (2.5I mL, 2H.41 mmol), and the reaction was stirred at 23°C in the dark for 18 hours. The mixture was poured into aqueous NaHS03. the solution was made basic with Na2C03, and extracted with 3x ethyl acetate, and the extracts were washed with brine, dried over Na2S04, to and condensed. The product was recrystallized From ethanol/ethyl acetate, to yield 5.~0 g (77%) of the desired compound.
MS (DCI (NH3) m/z 307 (M+NH4)+.
Examlale 152B
t5 To a solution of the product from Example 152A (1.4U g, 4.H26 mmol) in THF
(40 mL), water (10 mL), and methanol (10 mL) was added LiOH~water (4()5 mg, 9.65 mmol), and the reaction was stirred for 18 hours. The mixture was poured into 1 M HCI and extracted with 3x ethyl acetate, and the extracts were washed with brine, dried over Na2S04, and i;ondensed, to yield 1.23 g (92%) of the desired compound.
20 MS (DCI (NH3)) m/z 295 (M+NI-14)+.
Example 152C
To a solution of the product from Example 152B (440 mg, 1.6() mmol), in toluene (25 mL) was added oxalyl Chloride (0.140 mL, 1.6 mmol), and the reaction was stirred at KO °C for 25 1?( hours. The toluene was boiled off until HC1 evolution ceased, and the reaction was then cooled. Aniline ( 1 mL, 1 1 mmol) was added. and the reaction was stirred for 10 min, nad poured into 1 M HCI. The solution was extracted with 3x ethyl acetate, and the extracts were washed with brine, dried over Na2S04, and condensed, to yield 560 mg (99%) of the desired compound.
3U MS (DCI (NH3)) m/z 370 (M+NH4)+.
Example 152D

SUBSTITUTE SHEET (RULE 26) The desired compound was prepared from Example 152C (408 mg, 1.16 mmol), furan-3-boronic acid (182 mg, 1.62 mmol) and the procedure of Example 578, to yield 220 mg (56%) of the desired compound.
MS (DCI (NH3)) m/z 356 (M+NH4)+.
Example 152E
6-(aminoiminomethyl)-4-f3-furanyl)-N-phenyl-2-nanhthalenecarboxamide monoh,Lochloride The desired compound was prepared from Example 152D and the procedure of Example 40D.
W MS (DCI/NH3) m/z 356 (M+H)+;
~H NMR (300 MHz, DMSO-d~) 8 7.15 (m, 2H), 7.41 (dd, 2H), 7.83 (d, 2Hj, 7.91 (d, 1H), 7.99 (dd, 1 H), 8. I 9 (d, 1 H), 8.38 (s, 1 H), 8.41 (d, 1 H), 8.62 (s, 1 H), 8.69 (s, 1 H), 9.15 (br s, 2H), 9.55 (br s, 2H);
Anal. calc'd for C22H~~N30y2.75 HC1: C, 57.99; H, 4.37; N, 9.22. Found: C, 57.85; H, IS 4.84: N. 9.44.
Example 153 6-(aminoiminomethvl)-4-I 1-(methylsulfonyll-1 H=pvrazol-4-yll-N~hen nanhthalenecarboxamide monohydrochloride Example 153A
The desired compound was prepared from the product from Example 53D and the product from Example 152A by the procedure of Example 47A.
MS (DCI/NH~) m/z 4()8 (M+H)+.
,;
Example 153B
The desired compound was prepared from the product from Example 153A, by the procedure of Example 53F.
MS (DCI/NH3) m/z 278 (M+H)+.
3t1 Example 1530 The desired compound was prepared from the product from Example 153B, by the procedure of Example 87A (86A).
MS (DCI/NH3) m/z 373 (M+NH4)+.

SUBSTITUTE SHEET (RULE 26) Example 153D
The desired compound was prepared from the product from Example 153C, by the procedures of Example s 152B and 152C
MS (DCI/NH3} m/z 356 (M-S02Me+NH4)+.
Example 153E
6-(aminoiminomethyl)-4-fl-(meth ls~n l~l-IH-p~rrazol-4-vll-N-phenyl-2 naphthalenecarboxamide. monohydrochloride 1o The desired compound was prepared from Example 153D and the procedure of Example 4UD.
MS (DCI/NH3) NONE ;
IH NMR (300 MHz, DMSO-d~) 8 3.99 (s, 3H), 7.14 (t, 1H), 7.40 (t. ZH), 7.54 (d, 2H), 7.91 (d, 1 H), 5.05 (s, 1 H), 5.15 (d, I H), 5.35 (m. 2H), X.65 (br s, 2H), 9.33 (br s, 2H), 9.fi 1 (br s, 2H), 10.56 (s, 1 H);
Anal. calc'd for C22HtyN5S03~2.75 HCI: C, 49.51; H, 4.11; N, 13.12. Found: C, 49.44; H, 3.53; N, 12.09.
Exat~ple 154 2U 6-(aminoiminomethvl)-4-jS-(methylthio)-3-furanvlll-N=phenyl-~-nanhthalenecarboxamide mono~rdrochloride Example 154A
To a solution of 2-trimethylsilyl-3-bromofuran (4.17 g, 19.03 mmol) in THF (40 mL) ?S at -78°C was added a 1.5 M solution of LDA (12.7 mL, 19.03 mmol), and the reaction was stirred at -78°C for 1 hour. Methyl disulfide (1.89 mL, 20.93 mmol} was then added, and the reaction was allowed to warm to room temperature overnight. The reaction was poured into saturated aqueous NH4Cl solution, and extracted with 3x diethyl ether. The combined extracts were washed with brine, dried over Na2S04, and condensed. The crude material was 30 chromatographed on Si02 using hexanes as eluent, to yield 3.02 g (60%) of the desired compound.
MS (DCI/NH3) m/z 265, 267 (M+H)+.
Example 154B

SUBSTITUTE SHEET (RULE 26) A solution of the product from Example I54A (2.68 g, 10.1 mmol) and a I M
solution of TBAF (20.2 mL} in THF (20 mL) was stirred for 30 minutes. The reaction was condensed and The desired compound was chromatographed on Si02 using hexanes as eluent, to yield 1.39 g (71 %) of 2-methylthio-4-bromofuran. This material was taken on directly to the next step. To a solution of this product (7 mmol) in THF (25 mL) at -78°C
was added a 2.5 M
solution of BuLi (2.fi mL. 7 mmol), and the reaction was stirred for 5 minutes. Bu3SnCl (1.90 mL, 7 mmol} was then added, the reaction was stirred for 30 min, and then allowed to warm to room temperature. The reaction was poured into saturated aqueous NH4C1 solution, and extracted with 3x diethyl ether. The combined extracts were washed with brine, dried over 1U Na2S04, and condensed. The crude material was chromatog~raphed on Si02 using hexanes as eluent, to yield 1.24 g (30%) of the desired compound.
MS (DCI/NH3) m/z 404 (M+H)+.
Exam le 154 A solution of the product from Example 154B (920 mg, 2.28 mmol), the product from Example 152A (662 mg, 2.28 mmol}, and PdCl2 (PPh3)2 ( I61 mg, 0.23 mmol) in CH3CN ( 15 mL) was stirred for 18 hours at 80°C. The reaction was condensed and the crude material was chromatographed on Si02 using 20% ethyl acetate/hexanes as eluent, to yield 671 mg (91 °lo) of the desired compound.
2U MS (DCl/NH3) m/z 324 (M+H)+.
Example 154D
The desired compound was prepared from the product from Example 154C, by the procedure of Example 152 B.
MS (DCI/NH3) m/z 310 (M+H)+.
Example 154E
The desired compound was prepared from the product from Example 154D, by the procedure of Example 152C.
3u MS (DCI/NH3) m/z 402 (M+NH4)+.
Example 154F
6-(aminoiminomethvl)-4-15-(methvlthio)-3-furan 11~N-_phenyl-2-naphthalenecarboxamide mono~drochloride SUBSTITUTE SHEET (RULE 26) The desired compound was prepared from Example 1 S4E and the procedure of Example 144C.
MS (DCI/NH3) m/z 402 (M+H)+;
1 H NMR (300 MHz, DMSO-d6) 8 2.54 (s, 3H), 7.15 (t, 1 H), 7.24 (s, I H), 7.40 (t, 2H), 7.84 (d, 2H), 7.92 (dd, 1H), 8.19 (d, 1H), 8.39 (d, 1H), 8.44 (s, 1H), 8.61 (s, iH), 8.69 (s, IH), 9.35 (br s, 4H), 1().61 (s, 1H);
Anal. calc'd for C23H19N3S02~2.25 HCI: C, 57.14; H, 4.43; N, 8.69. Found: C, 57.13; H, 4.21; N, 8.56.
Exam lp a 15S
methyl f7-(aminoiminomethyl)-I-naphthalenvllmeth~rlcarbamate mono(trifluoroacetatel (salt) The desired compound is prepared according to the procedures described in Example s 12 and 13. Yield: 40 mg (42~%) of white solid t5 MS m/z: 258 (M+H)+
~H NMR (DMSO, 300 MHz): 3.28 (s, 3H), 3.82 (br, 3H), 7.66 (dd, 1 H, Jl=7.5 Hz, J2=1.4 Hz), 7.78 (m, 1 H), 8. 89 (Dd, I H, J 1=8.8 Hz, J2=2.0 Hz), 8.05 (d, I H, 8.1 Hz), 8.24 (d, I
H, 8.8 Hz), 8.30 (s, 1 H), 9.09 (s, 2H), 9.52 (s, 2H);
Anal. calc'd for C14H15N302. 1.25 C2F302H~0.25 H20: C, 49.02; H, 4.18; N, 10.39.
Found: C, 48.81; H, 3.91; N, 10.1 S.
Exam IR a 156 ~roovl f7-(arninoiminometh 1)-1-na hthalenyllcarbamate mono(trifluoroacetate)(salt) 2S The desired compound is prepared according to the procedures described in Example s 12 and 13. Yield: 52 mg (46~~c) of white solid MS m/z: 272 (M+Hj+
~ H NMR (DMSO, 300 MHz): 0.97 (t, 3H, J 1=J2=7.1 Hz), 1.67 (Sextet, 2H, J=7.1 Hz), 4.19 (t, 3H, J 1=J2=6.8 Hz). 7.71 (d, I H, 8.S Hz), 7.83 (m, 3H), 8.14 (d, 1 H, J=8.5 Hz), 8.67 3o (s, 1H), 9.22 (Br, 3H), 9.63 (s. 1H);
Anal. calc'd for C15H17N302. 0.25 C2F302H~0.75 H20: C, 49.18; H, 4.66; N, 9.83. Found:
C, 49.27; H, 4.87; N, IO.U2.
Example 1 S7 SUBSTITUTE SHEET (RULE 26) N-f7-(aminoiminomethyl_)-1-naphthalenyll-N'-meth~iurea mono(trifluoroacetate~(salt) The desired compound is prepared according to the procedures described in Example s 12 and 13. Yield: 36 mg (S4%) of white solid MS m/z: 243 (M+H)+
S ~H NMR (DMSO. 300 MHz): 2.80 (d, 1H), 6.45 (d, 1H), 7.70 (m, 2H), 7.82 (dd.
Jl=8.9 Hz. J2=2.1 Hz), 8.08 (dd, 7.4 Hz, J=1.3 Hz), 8.17 (d, 1 H, J=8.S Hz), 8.62 (s, 1 H), 8.72 (s, 1 H), 9.07 (s, 2H), 9.47 (s, 2H), (s, 2H);
Anal. calc'd for C13H14N4O. 1.S C2F302H~O.S H20: C, 45.50; H, 3.94; N, 13.27.
Found:
C, 45.22; H, 3.86; N, 13.12.
Example 1S8 ethyl 17-(aminoiminomethyl)-1-naphthalen rLl)carbamate mono(trifluoroacetate)(salt) The desired compound is prepared according to the procedures described in Example s 12 and 13. Yield: 70 mg (76%) of white solid ~5 MS m/z: 2S8 (M+H)+
1H NMR (DMSO, 300 MHz): 1.30 (t, 3H, Ji=J2=7.4 Hz), 4.20 (q, 2H, J=7.0 Hz), 7.80 (m, 4H), 8.1 S (d, 8.S Hz), 8.68 (s, 1 H), 9.13 (s, 2H), 9.38 (s, 2H), 9.66 (s, 1 H);
Anal, calc'd for C~4H15N302~1.5 C2F302H: C, 47.67; H, 3.88; N, 9.81. Found: C, 47.97;
H, 3.85; N, 9.78.
Example 159 N-17-(aminoiminomethyl)-1-naphthalenvl)probanamide monoltrifluoroacetatel(saltl The desired compound is prepared according to the procedures described in examples 12 and 13.
Yield: 2t) mg (23 % ) of white solid MS m/z: 242 (M+H)+
1 H NMR (DMSO, 3()0 MHz): 1.18 (t, 3H, 7.4Hz), 3.38 (m, 2H), 7.89 (m, 3H), 7.81 (dd, I H, J I=8.4Hz, J2=1.9 Hz), 7.87 (d, 1 H, 8.S Hz), 8.58 (s, 1 H), 9.02 (s, 2H), 9.47 (s, 2H), 9.97 (s, i H).
3u Anal. calc'd for C ~4H 15N30. 1. I S C2F302H . 0.25 H20: C, 51.94; H, 4.45;
N, 11.15;
Found: C. 52.02; H, 4.24; N, 10.76.
Exam le 16 SUBSTITUTE SHEET (RULE 26) N-f7-laminoiminomethvl)-I-nanhthalenvl)-2-methoxyacetamide monoltrifluoroacetate)( alt) The desired compound is prepared according to the procedures described in Example s 12 and 13. Yield: 30 mg (30%) of white solid MS m/z: 258 (M+H)+
s 1H NMR (DMSO, 300 MHz): 3.49 (s, 3H), 4.I8 (s, 2H), 7.80 (m, 3H), 7.93 (d, I
H, 7.7 Hz), 8.47 (d, I H, 8.5 Hz), 8.47 (s, 1 H), 9.10 (s, 2H), 9.46 (s, 2H), 9.99 (s, 2H);
Anal. calc'd for C14H15N302~1CZF302H~1.25 H20: C, 48.80: H, 4.73: N, 10.67.
Found: C, 48.53; H, 4.34; N, 10.54;
~ H NMR (DMSO, 300 MHz): 2.16 (s, 3H), 4.85 (s, 2H), 7.82 (m, 4H), 8.18 (d, I
H, J=8. I8 ~0 Hz), 8.55 (s, 1 H), 9.10 (s> 2H), 9.44 (s, 2H), 10.24 (s, 1 H);
Anal. calc'd for C15H15N3O3~1C2F302H~1 H20: C, 48.93; H, 4.35; N, 10.07.
Found: C, 48.82: H, 4.27; N, 10.00.
Example 161 15 N-f7-(aminoiminomethvl)-1-naphthalenyllurea mono(trifluoroacetate)(salt) The desired compound is prepared according to the procedures described in Example s 12 and 13. Yield: 35 mg (54%) of yellownish solid MS m/z: 229 (M+H)+
tH NMR (DMSO, 300 MHz): 6.22 (s, 2H}, 7.65 (m, 2H), 7.77 (dd, JI=8.8 Hz, J2=I.SHz).
20 8.57 (s, 1 H), 8.79 (s, 1 H), 9.07 (s, 2H), 9.49 (br, 2H);
Anal. calc'd for C22Ht2N40. 1 CZF302H~0.75 H20: C, 40.90; H, 3.33; N, I 1.95.
Found: C, 40.95; H, 3.64; N, 12.31.
Exam! la a 162 25 N-17-(aminoiminomethvl)-1-naphthalen 1y~1~2-hydroxvacetamide mono(trifluoroacetate)(saltl The desired compound is prepared according to the procedures described in Examples 12 and 13. Yield: 24 mg (37%) of white solid MS m/z: 244 (M+H)+
~H NMR (DMSO, 300 MHz): 4.18 (s, 2H), 5.82 (br, 1H). 7.67 (m, 1H), 7.85 (m, 3H), 8.20 3U (d, 1 H), 9. I 8 (s, 2H), 9.42 (s, 2H), 9.89 (s, 1 H);
Anal. calc'd for C~3H13N302~1 C2F302H~0.75 H20: C, 48.59; H, 4.21; N, 11.33.
Found: C, 48.64: H, 3.89; N, I 1.25.
Example 163 SUBSTITUTE SHEET (RULE 26) 8-l2-pyrimidinylamino)-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) The desired compound is prepared according to the procedures described in Examples 91 A and l3.Yield: 28 mg (28%) of pale yellow solid MS m/z: 264 (M+H)+
S 1H NMR (DMSO, 300 MHz): 6.90 (t, IH, J1=J2=4.7 Hz), 7.69 (d, J=7.8 Hz), 7.80 (1 H, J=8. I Hz), 7.81 ( 1 H, dd, J 1=8.4 Hz, J2=2.1 Hz), 8.08 ( 1 H, dd, J 1=7.4Hz, J2=0.6 Hz), 8.14 (1H, d, J=8.5 Hz), 8.49 (d, 2H), 8.75 (1H, d, 3=1.7 Hz). 9.06 (s, 2H), 9.37 (s, 2H), 9.6U (s, l H);
Anal. calc'd for Ct5H13N5. 2.25 C2F302H~0.25 H20: C, 44.67; H, 4.283.03; N, 13.36.
icy Found: C> 44.49; H, 2.80; N, 13.40.
Example 164 H-amino-2-naphthalenecarboximidamide bis~trifluoroacetate)(,sal>;~
To a solution of crude 8-amino-2-nitrile-naphthalene prepared as described in Example t 5 1 () at room temperature in 10: I pyridine: triethylamine ( 10 mL) was bubbled hydrogen sulfide for 5 minutes and stirred at room temperature overnight. The reaction mixture was added water (50 mL) and the product was extracted into ethyl acetate (3x30 mL) . The combined organic solvent was dried over magnesium sulfate, filtered and evaporated. The resulting yellow substance was taken up in acetone (30 mL} then added methyl iodide (2 mL). The reaction 2t> mixture was boiled for 1 hour, then evaporated to dryness. To the resulting yellow substance in methanol (25 mL) was added ammonium acetate ( 100 mg) and stirred at room temperature overnight. The solvent was removed under vacuum and the product was purified via reverse phase chromatography using 0.1 ~lo TFA/water and 0.1 ~lo TFA/methanoE as eluent.
MS m/z: 186 (M+H)+
25 t H NMR (DMSO, 300 MHz): 5.14 (br, 3H), 6.80 (dd, 1 H, J 1=7.8 Hz, J2=1 Hz), 7.17 (d, I H, J=7.8 Hz}, 7.40 (dd, I H, J 1=J2=7.8 Hz), 7.70 (dd, 1 H, J 1=8.9 Hz, J2=2. I Hz), 7.91 (d, IH, J=8.5 Hz), 8.65 (s, 1H), 8.95 (s, 2H), 9.23 (s, 2H);
Anal. calc'd for CI tHt 1N3~2.5 C2F302H~0.75 H20: C, 39.72; H, 3.13; N, 8.69.
Found: C, 40.01; H, 3.19: N, 8.88.
Exam I~ 1 fi5 6-(aminoiminomethvl)-N-14-(aminometh ~Lll~~ll-4-(~-~vrimidin~rlamino)-2 n~phthalenecarboxamide tris(trifluoroacetate)( a~) SUBSTITUTE SHEET (RULE 26) Example 165A
A suspension of 2-nitrite-6-methyester naphthalene Example 8D (5.0 g, 23 mmol) in concentrated sulfuric acid (50 mL) at -5 °C was added a solid potassium nitrate. The colour of reaction mixture was gradually changed into a dark brown. The reaction mixture was stirred for I 5 minutes and was poured into ice-water. Collected the precipitate and washed with water. The crude product was recrystallized from ethyl acetate and ethanol. Yield 4.3 g (68%) of pale yellow powder.
Example 165B
to To a solution of 2-nitrite-6-methylester-8-vitro-naphthalene, Example 165A
(3.5 g, 13.6 mmol) in a mixture of THF ( 100 mL) and ethyl acetate ( 120 mL) was added 10%
Pd-C (350 mg). The reaction mixture was placed under hydrogen at atmospheric pressure (balloon) and stirred at room temperature for 3 5 hour. The mixture was filtered through celite and silica gel, washed with ethyl acetate and evaporated. The resulting solid was washed with ether (20 mL).
~ 5 Yield 2.20 g {7 I °lo) of yellow powder.
Example 165 A mixture containing 2- Nitrite-6-methylester-8-amino-naphthalene, Example 165B (2.8 g, 12.3 mmol), BINAP ( 116 mg, 0.186 mmol), Pd2 (DBA)3,64 mg, 0.061 mmol), Na0-t-Bu 20 ( 1.667 g, 17.6 mmol), 2-Brornopyrimidine (2.363 g, 14.9 mmol) and Toluene (80 mL) in an oven-dried flask under nitrogen, was stirred at room temperature for 10 minutes. The reaction mixture was heated to HO'C for 1 hour. At the end of the reaction (TLC, hexanes+ethyl acetate=4: 1 ), brine 9200 mL) was added. Extracted the mixture with CH2Cl2.
(4x250 mL).
Evaporated the solvent. Yield 3.~ g (93%) of pale yellow powder.
Example I65D
TO a suspension of 2-nitrite-6-methylester-8-N- (2-pyrimidine)-naphthalene, Example 165C (5.2 g, 17.1 mmol ) in ethanol ( 150 mL) was added potassium carbonate (3.54 g, 33.3 mmol j in water (200 mL). The resulting suspension was heated at 120 °C
for 2 hours, at that 3~ time all the suspension turned into a clear solution. The mixture is cooled down, then acidified with 2 N HCI. The resulting precipitate was collected by filtration to yield 4.5 g (90%) of pale yellow powder. No further purification was required for the next step.
Example 165E

SUBSTITUTE SHEET (RULE 26) To a cold (0°C) solution of 2-nitrite-8-N- (2-pyrimidine)-6-carboxylic acid-naphthaleneExampIe I65D (5.0 g, 17.2 mmol) in DMF ( 150 mL) was added DIEA
(7.6 mL, 42.6 mmol) and O- (7-Azabenzotriazol-1-yl)-N, N, N', N'-tetramethyluroniumhexafluorophosphate (9.8 g, 25.7 mmol) followed by tert-S Butoxycarbonylamino-4-aminomethylaniline (5.74 g, 20 mmol). The resuting reaction mixture was stirred for about 1 hour. The reaction was quenched with water (200 mL) and the resulting precipitate was collected by filtration to yield 3.26 g (38%) of pale yellow powder.
Example 165F
t0 To a solution of the substrate, Example I65E (3.0 g, 6.07 mmol) in pyridine (150 mL) was added triethylamine (9 mL). H2S was passed for 10 minutes and the resultiing mixture was stirred at room temperature for 48 hour. 100 mL of water was added to the reaction mixture and the precipitate was Collected by filtration. Yield (3.0 g (93%) of yellow solid.
S Example 1656 To a solution of the thioamide, Example 165F in acetone (200 mL) was added Mel (6 mL) and the mixture was stirred at room temperature overnight. The mixture was evaporated to dryness to yield 1.2 g (78%) of yellow solid.
2U Example 165H
6-(aminoiminornethvl)-N-f4-(aminomethyl henyll-4-(2-p~rimidinvlamino)-2 n~,phthalenecarboxamide tris(trifluoroacetate)lsalt) To a solution of the imidate ester, Example 1656, (1.5 g, 2.2 mmol) in methanol (50 mL j was added ammonium acetate (0.5 g, 6.4 mmol) and stirred at room temperature 25 overnight. After evaporation of the solvent the residue was treated with ether (3x25 mL) and the ether was decanterd out. The residue was dissolved in a mixture of 10: l: 1 acetonitrile: water:
acetic acid (50 mL). After addition of ether ( 100 ml.j, the Boc protected product precipitated as an acetate salt and was colIeted by filtration. The solid was added 1: I TFA:
methylene chloride (50 mL) containing thioanisole (0.5 mL). The reaction mixture was stirred at room temperature 30 overnight. The product was purified over RPCtg chromatography using water:
methanol with 0.1 °lo TFA as eluent. Yield after lyophilization 0.5 g (54%) of pale yellow solid.
MS m/z: 412 (M+H)+
tH NMR (DMSO, 300 MHz): 4.02 (q, 2H, J=5.8), 6.94 (dd, 1H, JI2=J2=4.8 Hz), 7.45 (d, 2H, J=8.5 Hz), 7.84 (d, 2H, J=8.4 Hz), 7.92 (dd, IH, 31=8.5 Hz, J2=1.7 Hz), 8.13 (br, SUBSTITUTE SHEET (RULE 26j 3H), 8.30 (d. 1 H, J=8.9 Hz), 8.41 (s, 1 H}, 8.52 (d., 2H), 8.55 (s, 1 H), 8.8 i (s, I H), 9.19 (s, 2H), 9.43 (s, 2H), 9.75 (s, 1H), 10.62 (s, 1H):
Anal. calc'd for C23H21N70~2.5 C2F302H~1 H20: C, 43.49; H, 3.22; N, 11.83.
Found: C, 43.54; H, 3.34; N, 11.69.
S
Example 166 6-laminoiminomethvl)-N-phenyl-4-l2-pyrimidi~lamino)-2-nanhthalenecarboxamide monoftrifluoroacgtate) (salt) The same procedure as described in Examples 165 substituting aniline for 4-amino l0 benzyl amine.
MS m/z: 383 (M+H)+
~ H NMR (DMSO, 300 MHz): 6.93-6.96 (m, 1 H), 7.14 (dd, 1 H, J I=7.3 Hz, J2=7.4 Hz), 7.40 (dd, 2H, J1=J2=7.3 Hz}, 7.80 (, d, 2H, J=8.1 Hz), 7.91 (d, 1H, J=8.9 Hz), 8.30 (d, 1 H, J=9.0 Hz), 8.41 (s, 1 H), 8.52-8.54 (m, 3H), 8.80 (s, 1 H), 9.16 (s, 2H), 9.45 (s, 2H), t 5 9.78 (s, 1 H), 1 ().55 (s, 1 H);
Anal. calc'd for C22HtgN~,0~2 CZF302H~0.25 H20: C, 50.78; H, 3.28; N, 13.31.
Found: C, 50.85; H, 3.28; N, 13.31.
Example 167 2o N-f(4-(aminomethvl)phenvll-6-lamino(hvdroxyimino)methyil-4-(2-pyrimidinylamino)-2-naphthalenecarboxamide bis(trifluoroac fate, (salt) To a suspension of compound, prepared in Example 165 E (0.20 g, 0.40 mmol ) in methanol (40 mL) and water (20 mL) was added hydroxylamine hydro-chloride ( 1 I 2 mg, I .75 mmol) and sodium carbonate (85 mg, 0.80 mmol), the reaction mixture was stirred for 48 25 hours at room temperature, TLC showed no reaction. Th reaction mixture was heated at reflux for 1() hours and removed the most of the solvents, the precipitate was collected by filtration, gave 1.2 g of pale yellow solid. The solid was disoolved in 1: 1 TFA+CHzCl2 (30 mL) and sitrred at room temperature for 24 hours. The solvents was removed under vaccuum and the residue was loaded to a R I 8 reverse phase column. The fraction was lyophilized and yielded a 3tt pale yellow powder (80 mg, 66°~0).
MS m/z: 428 (M+H)+
t H NMR (DMSO, 300 MHz): 4.02 (q, 2H, J=6.1 Hz), 6.92 (dd, 1 H, J I=J2=5.1 Hz), 7.46 (d, 2H, 8.4 Hz), 7.85 (d, 2H, J=8.5 Hz), 7.88 (d, IH, 9Hz), 8.12 (br, 3H), 8.22 (d, 1H, J=8.9 Hz), 8.40 (s, SUBSTITUTE SHEET (RULE 26) ~H ), 8.48 (s, 1H), 8.51 (d, 2H, J=4.8 Hz), 8.64 (s, 1H), 9.74 (s, 2H), 10.61 (s> 2H);
Anal. calc'd for C23H2tN~02~2.9 C2F302H~1.25 H20: C, 44.31; H, 3.41; N, 12.56;
F, 21.17 Found: C, 44.08; H, 3.30; N, 12.50, F, 21.25.
Example 168 6-(aminoiminomethyl)-N-f4-(hvdroxymethyl)phenvll-4~2 ~yrimidinylamino) 2-naphthalenecarboxamide, mono(trifluoroacetate)(salt) The desired compound is prepared as described in Example 165 using 4-amino benzyl alcohol instead of 4-amino benzylamine.
t0 MS m/z: 413 (M+H)+
iH NMR (DMSO, 300 MHz): 4.48 (s, 2H), 6.94 (dd, 1H, 2H, J=8.8 Hz), J1=J2=4.8 Hz), 7.32 (d, 2H, J=8.8 Hz), 7.90 (dd, 1 H, J 1=8.5 Hz, J2=1.7 Hz), 8.28 (d, 2H, J=8.8 Hz), 8.41 (s, 1H), 8.54 (d, 2H, J=4.8 Hz), 8.55 (dd, 1H, J=1.3 Hz), 8.80 (s, 1H), 9.08 (s, 2H), 9.43 (s, 2H), 9.73 (s, 1 H), 10.48 (s, 1 H);
Anal. calc'd for C23H20N~,02: C, 49.06; H, 3.83; N, 12.81; F, 16.50. Found: C, 48.74; H, 3.86; N, 12.63, F, t 6.54.
Example 170 methyl f3-fff4-(aminometh~phenyllaminolcarbon~Jl-7-j4-amino(hydrox imino)methyll-1-naphthalenvllcarbamate, bis(trifluoroacetate)(saltl Example 170A
To a suspension of the nitrile, Example 14I D (213 mg, 0.45 mmol) and hydroxylamine hydrochloride (338 mg, 4.86 mmol) in methanol (40 rnL) water (5 mL) was added potassium carbonate (53R mg, 3.9 mmol) stirred at room temperature overnight. The solvent was evaporated and the resulting solid was washed with ether and hexanes to yield the product as white solid 153 mg (62~1~ ).
MS (ECI) m/z 508 (M+H}+.
Example 1708 methyl f3-fff4-(aminomethyl)nhenvllaminolcarbonvll-7-f4-amino(hydroxyimino)methyll 1-naphthalenyllcarbamate bis(trifluoroacetate)(salt) The Boc protected substrate, Example 170A was added 3 mL of 4 N HCI in dioxane and stirred at room temperature for 20 minutes. The solvent was evaporated under vacuum and SUBSTITUTE SHEET (RULE 26) the product was separated on MPLC with a column of RP Clg using methanol-water +0.1%TFA as eluent. Yield of white solid 117 mg (79%).
MS (ECI) m/z 408 (M+H)+;
~ H NMR (300 MHz, DMSO-d~,) 8 3.77 (S, 3H), 4.03 (s, 2H), 4.01 (q, J=5.9 2H), 7.46 (d, J=B.SHz. 2H), 7.86 (d, J=8.SHz, 2H), 7.90 (dd, JI=8.5, Hz, J2=l.4Hz, IH), 8.09-8.15 (m, 4H), 8.17 (d, J=8.4Hz, I H), 8.29 (s, 1 H), 8.42 (s> I H), 8.56 (s, 1 H), 9.80 (s, I H), 10.62 (s, 1H);
Anal. calc'd for C21 H21 N504~2.5 TFA~0.5 H20: C, 44.52; H, 3.52; F, 20.31; N, 9.98.
Found: C, 44.78; H, 3.57; F, 19.82; N, 9.87.
Exam I~e 171 6-Iamino(hydroxyimino)methyll-N- henyl-2-naDhthalenecarboxamide The title compound is prepared as described by Judkins et al., Synthetic Communications 26 (23), 4351-4367 ( 1996). The compound prepared in Example 55C (0.1 a g, .36 mmole) is dissolved in a 30: 1 mixture of Toluene: methanol to which is added hydroxylamine hydrochloride (3.6 mmole) and potassium tent-butoxide (3.6 mmole). The resulting slurry is refluxed for I7 hr., cooled, solvents removed under vacuum. The residue is taken up in distilled water (30 ml) extracted with ethyl acetate (2 X 100 ml).
The combined organic extracts are washed with 10% NaCI (50 rnl), dried over anhydrous Na2S04. The 2o sample is filtered of drying agent and the solvent removed under vacuum leaving a white solid (65 mg). The material is purified by medium pressure reverse phase chromatography as described in Example 1. The title compound is obtained as white solid (45 mg) MS (m/z) M + H+: 306 ~ H NMR (DMSO-d6): 10.51 (s, 1 H), 9.32 (s, OH), 8.70 (s, 1 H), 8.57 (s, 1 H), 8.34 (d, I H), 25 8.25 (d, 1 H), 8.17 (dd, 1 H), 7.90 (dd, 1 H), 7.83 (d, 2H), 7.40 (dd, 2H), 7.15 (dd, 1 H), 6.25 (bs, 2H).
Analysis: calc'd for C2~H1~,N304 F3: C, 57.28, H, 3.85, N, 10.02; Found C, 56.89, H, 3.65, N, 9.90.
=t~ Example 174 8-(2-DVridinvlamino)-2-nanhthalenecarboximidamide bisftriffuoroacetate) salt Example 174A

SUBSTITUTE SHEET (RULE 26) To a solution of the product from 11 D ( 1 b8 mg, 1.00 mmol) in 5 mL toluene was added 2-bromopyridine (0.105 mL, I.1 mmol), NaOtBu ( 135 mg, 1.4 mmol), Pd2dba3 (92 mg, 0.1 mmol), and P (o-tolyl)3 (122 mg, 0.4 mmol), and the reaction was stirred for 24 hours at 100 °C. The reaction was cooled, and the crude reaction mixture was chromatographed on Si02 S using 50% ethyl acetate/hexanes as eluent to yield 80 mg (33%) of the desired compound.
MS (DCI (NH3)) m/z 246 (M+H)+.
Example 174B
R_-12-yvridinvlamino)-2-naphthalenecarboximidamid bi ( 'fluoroacetate) salt 1o The product from Example 174A (121 mg, 0.493 mmol) was dissolved in THF (2 mL) and 0.543 mL of a 1 M solution of LiN (TMS)2 in THF was added. The reaction was stirred for 5 min, and TMSCI (0.069 mL, 0.543 mmol) was added. After stirring for 30 min, another 1.09 mL of the 1 M solution of LiN (TMS)2 was added. The reaction was stirred for 18 hours, and 10 mL of a 2 M aq. HCl solution was added. The reaction was stirred for another 24 hours.
IS and was basicified with saturated aq. Na2C03. The mixture was extracted with 3x ethyl acetate, and the extracts were washed with brine, dried over Na2S04, and condensed. The crude product was purified by reverse-phase HPLC to yield the desired compound (21 mg, 7%): m.p.
I 37-147 °C.
MS (DCI (NH3) m/z 263 (M+H)+;
2U 1 H NMR (300 MHz, DMSO) S 9.98 (br s, 1 H), 9.46 (br s, 2H), 9.27 (br s, 2H), 8.74 (s, 1 H), 8.21 (d, J=9 Hz, I H), 8.1 1 (d, J=6 Hz, 1 H), 8.02 (d, J=9 Hz, 1 H), 7.8 I -7.95 (m, 3H), 7.75 (dd, J=9, 9 Hz, 1H), 7.16 (m, 1H), 6.95 (m, 1H), 2.55 (s, 3H);
Anal. calc'd for CI~H14N4~3.IC2HF302: C, 43.30; H, 2.80; N, 9.10. Found: C, 43.14; H, 3.04; N, 9.90.
Example 176 fi-I4-l(hvdroxvmethvl)Dhenvllmethoxvl-2-nanhthalenecarboximidamide methanesulfonatei~alt) Example 176A
To a solution of NaH (b0% in mineral oil, 1.17 g, 29.3 mmol) in THF (50 mL) was added 4-bromobenzyl alcohol (5.22 g, 27.9 mmol) in THF (50 mL), and the reaction was stirred at room temperature for 20 minutes. p-Methoxybenzyl chloride (4.07 mL, 30 mmol) was then added, and the reaction was stirred at 50°C for 2 hours. The mixture was poured into water and extracted with 3x diethyl ether, and the extracts were washed with brine, dried over SUBSTITUTE SHEET (RUtE 26) WO 99!05096 PCTIU598/15386 Na2S04, and condensed. The crude reaction mixture was chrornatographed on Si02 using hexanes as eluent, to yield 7.39 g (86%) of the desired compound.
MS (DCl (NH3)) m/z 326 (M+NH4)+;
!H NMR (300 MHz, CDCl3) 8 7.47 (d, 2H), 7.28 (d, 2H), 7.23 (d> 2H), 6.90 (d, 2H)> 4.48 (s, 3H), 4.47 (s, 2H), 3.91 (s, 3H).
Example 176B
To a solution of the product from Example 176A (6.80 g, 22.13 mmol) in THF ( mL) and hexanes (20 mL) at -100°C was added a 2.5 M solution of BuLi (8.85 mL, 22.13 !0 mmol), and the reaction was stirred for 2 minutes. DMF (3.43 mL, 44.3 mmol) was then added, and the reaction was warmed to room temperature. The mixture was poured into water and extracted with 3x diethyl ether, and the extracts were washed with brine, dried over Na2S04, and condensed. The crude reaction mixture was taken up in methanol ( 100 mL) and NaBH4 ( 1.0 g, 26.2 mmol) was added in portions. A few drops of water were added, and the !5 mixture condensed. The residue was chromatographed on Si02 using 20% ethyl acetate/hexanes as eluent, to yield 3.32 g (58%) of the desired compound.
MS (DCI (NH3)) m/z 276 (M+NH4)+;
!H NMR (300 MHz, CDCI3) 87.38 (s, 4H), 7.29 (d, 2H), 6.90 (d, 2H), 4.70 (s, 2H), 4.54 (s, 2H), 4.49 (s, 2H), 3.81 (s, 3H), 1.62 (s, 1H).
Example 176C
To a solution of the product from Example 176B ( I 93 mg, 0.747 mmol), the product from Example 2HA ( I 39 mg, 0.822 mmol), and Ph3P (216 mg, 0.822 mmol) in THF
( 10 mL) at 0°C was added diethylazodicarboxylate (0.129 mL, 0.822 mmol), and the reaction was stirred for 90 minutes at room temperature. The crude reaction mixture was condensed, and the residue was chromatographed on Si02 using 10% ethyl acetate/hexanes as eluent, to yield 225 mg (74%) of the desired compound.
MS (DCl (NH3)) m/z 427 (M+NH4)+;
!H NMR (30U MHz, CDC13) 8 8.15 (s, IH), 7.81 (d, 1H), 7.77 (d> IH), 7.58 (dd, IH), 7.48 (d, 2H), 7.42 (d, 2H), 7.02-7.15 (m, 4H), 6.90 (d, 2H), 5.21 (s, 2H), 4.56 (s, 2H), 4.51 (s, 2H), 3.91 (s, 3H).
Examtale t 76D

SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCT/US98/1538( To a solution of the product from Example 176C (220 mg, 0.537 mmol) in CH2C12 (40 mL) and water (7 mL) was added DDQ (244 mg, 1.07 mmol), and the reaction was stirred for 90 minutes. The crude reaction mixture was taken up in CH2Cl2, washed with 2x aqueous NaHC03 and brine, dried over Na2S04, and condensed. The residue was chromatographed on Si02 using 50% ethyl acetate/hexanes as eluent, to yield 89 rng (57%) of the desired compound.
MS (DCI (NH3)) m/z 307 (M+NH4)+;
1 H NMR (300 MHz, CDCl3 ) 8 8.15 (s, 1 H}, 7.81 (d, 1 H), 7.77 (d, I H), 7.57 (dd, I H), 7.49 (d, 2H), 7.41 (d, 2H), 7.33 (dd, 1H), 7.21 (d, 1H), 5.21 (s, 2H), 4.74 (s, 2H), I.63 (br s, io 1 H); .
Example 176E
6-f4-f(hvdroxvmethvl)ohenvlimethoxvl-2-naphthalenecarboximidamide methane ulfonate~sal~
The desired compound was prepared from Example 176D and the procedure of Example ~s SSD.
MS (DCI/NH3) m/z 307 (M+H)+;
~ H NMR (300 MHz, DMSO-d~,) 8 2.31 (s, 3H), 4.52 (s, 2H), 5.25 (s, 2H), 7.37 (d, 2H), 7.39 (dd, 1 H), 7.47 (d, 2H), 7.59 (d, 1 H), 7.79 (dd, 1 H}, 8.00 (d, 1 H), 8.03 (d, I H), 8.4I
(s, I H), 8.89 (br s, 2H), 9.34 (br s, 2H);
20 Anal. calc'd for C~9H1gN202~1.15 CH4S03: C, 58.06; H, 5.46; N, 6.72. Found:
C, 58.24;
H, 5.62; N, 6.59.
Example 177 N-hvdroxv-8-(2-vvrimidinylaminol- 2-naphthalenecarboximidamide S mono(trifluoroacetate)(saEt~
The desired compound is prepared from the nitrile described in Example I63 and utilizing the procedure described in Example 167. Yield as a white powder: 50 mg MS m/z: 280 (M+H)+
30 ~ H NMR (DMSO, 300 MHz): 6.90 (dd, 1 H, J 1=J2=5.2Hz), 7.45 (m, 3H), 8.0 (d, 1 H, J=8.5 Hz), 8.14 (d, 1 H, J=8.4Hz), 8.49 (d, J=5.3 Hz), 8.61 (s, 1 H), 9.58 (s, 1 H);
Anal. calc'd for C15H13N50~2.0 C2F302H~0.5 H20: C, 44.20; H, 3.I2; N, 13.56.
Found: C, 44.24; H, 2.94; N, 13.49.

SUBSTITUTE SHEET (RULE 26) Exam lp a 179 6-(2-R~ylethynXll-2-naphthalenecarboximidamide mono(trifluoroacetate)( altl Example 179A
Using the product obtained in Example 28B, 2-ethynylpyridine (Lancaster Chemical Corp.) and the procedure described in Example 121 A, the desired compound was obtained.
MS (DCI/NH3) m/z 255 (M+H)+.
Examvle 179B
Using the product obtained in Example 179A and the procedure described in Example 94D the desired compound was obtained.
MS (DCI) m/z 272 (M+H)+;
~ H NMR (300 MHz, D MSO) & 7.45-7.50 (m, 1 H), 7.72 (d, 1 H), 7.82 (dd, 1 H), 7.86-7.92 (m, 2H), 8.1 H (d, I H), 8.22 (d, 1 H), 8.42 (s, 1 H), 8.54 (s, 1 H), 8.68 (m, 1 H), 9.25 (s, 2H), 9.49 (s, 2H);
Anal. calc'd for C20H ~4F3N302~0.25 H20: C, 61.62; H, 3.75; N, 10.78. Found:
C, 61.72;
H, 3.64; N, 10.66.
Example 180 6-(aminoiminometh lv )-N-N-phenyl-4-(tetrahydro-3-furanyl)-2-naphthalenecarboxamide monohydrochloride Examt~le 180A
The desired compound was prepared from the product from Example l 52 by the procedure of Example 62A.
MS (DCI/NH3) m/z 340 (M-H20)~.
Example 180B
The desired compound was prepared from the product from Example 180A by the 3~> procedure of Example 62B.
MS (DCI/NH3) m/z 343 (M+H)+.
Exam le 180 SUBSTITUTE SHEET (RULE 26) The desired compound was prepared from Example I80B and the procedure of Example SSD.
MS (DCI/NH3) m/z 360 (M+H)+;
~ H NMR (300 MHz, DMSO-d6) 8 2.20 (m, 1 H), 2.52 (m, 1 H), 3.85 (dd, 1H), 3.94 (ddd, 1H), 4.08 (ddd, lh), 4.26 (dddd, 1H), 4.39 (dd, 1H), 7.14 (t, 1H), 7.40 {t, 2H), 7.81 (d, 2H), 7.95 {d, 1 H), 8.08 (s, 1 H), 8.32 (d, 1 H), 8.59 (s, 1 H), 8.79 (s, 1 H), 9.25 (br s, 2H), 9.61 (br s, 2H);
Anal. calc'd for C22H21N302~2.6 HCI: C, 58.18; H, 5.24; N, 9.25. Found: C, 58.21; H, 4.91; N, 9.13.
Exam Ip a 181 6-famino(h droxyiminolmethyll-N-phenyl-4-(2-pvrimidinvlartin~l-2-naphthalenecarboxamide Prepared in a similar manner as described in Example 177 using the material prepared in Example 166.
t5 MS m/z: 399 (M+H)+
~ H NMR (DMSO, 300 MHz): 6.88 (dd. 1 H, 4.7Hz), 7.1 1 (dd, l H, J l=J2=7.SHz), 7.37 (dd, 2H, J 1=J2=7.5 Hz), 7.82 (d, 2H, J=8.8 Hz), 7.94 (dd, 1 H, J 1=8.SHz, J2=1.4 Hz), 8.04 (d, 1 H, J=8.8Hz), 8.31 (s, 1 H), 8.43 (dd, 1 H, J=14 Hz), 8.74 (d, 2H, J=4.7 Hz), 8.52 (s, 1 H), 9.55 (s, 1 H), 9.85 (s, 2H), 10.41 {s, 1 H);
2o Anal. calc'd for C22H~gN602~0.4 H20: C, 65.14; H, 4.67; N, 20.72. Found: C, 65.57; H, 4.45; N, 20.18.
Example 182 methvl 4-f f f 7-amino(hvdroxviminolmethyll-2-nanhthaIenvllo~imethvllbenzoate 25 The resulting product from Example 2I 3A ( 1 10 mg, 0.347 mmol), hydroxylamine hydrochloride (26.5 mg, 0.381 mmol), triethylamine (53 ftl, 0.381 mmol) and N, N-dimethylformamide (12 mL) were combined in a four inch glass pressure tube.
The tube was sealed and heated for 24 hours at 80 °C. The tube was cooled to room temperature and additional hydroxylamine hydrochloride (48.1 mg, 0.693 mmol) and triethylamine (96.6 ~,1, 30 0.693 mmol) in N, N-dimethylformamide (2 mL) was added. The tube was resealed and heated for 24 hours at 80 °C. The addition, as above, was repeated a second time, the tube was resealed and heated for 72 hours at 80 °C. The reaction mixture was concentrated to a solide residue which was purified by column chromatography on silica gel (60 g) eluted with 15%

SUBSTITUTE SHEET (RULE 26) acetone in methylene chloride to yield the target compound as a white solid (43 mg, 50% based on recovered starting material).
MS {DCI (NH3)) m/z 351 (M+H)+;
IH NMR NMR (300 MHz, DMSO-d6) 8 3.860 (s, 3H), 5.349 {s, 2H), 5.860 (s, 2H), 7.280 (dd, 1H), 7.381 (d, 1H), 7.660 (d, 2H)> 7.688 (dd, IH), 7.805 (d, 1H), 7.850 (d, 1H), 8.010 (d> 2H), 8.070 (s, 1H), 9.724 (s, IH);
Anal. calc'd for CZpH1gN204~0.15 H20: C, 68.04; H, 5.22; N, 7.93. Found: C, 68.06; H, 5.05; N, 7.87.
to Example 184 N-I4-(aminocarbonyl)phen,yll-6-(aminc~iminometh I)-2-naphthalenecarboxamide monoltrifluoroacetate) salt Ex~mole 184A
A suspension of the product obtained in Example 8A (30U mg, 1.39 mmol) and 5 mL
dichloromethane was added dropwise to a 0° solution of 4-aminobenzamide (207 mg, 1.52 mmol), triethylamine (0.44 mL, 3.2 mmol), and 10 mL dichloromethane. The reaction mixture was stirred for 0.5 hour at 0° and for I H hours at room temperature.
Excess ether was added with stirring and the resultant solid was filtered, washed with 1 N HCI, water, and was dried under vacuum to afford the desired compound.
MS (DCI) m/z 333 (M+NH3)+.
E~mule 184B
N-I4-(aminocarbonvl)phenvll-6-(aminoiminomethyl)-2-naphthalenecarboxamide monoltrifluoroacetate) salt Using the product obtained in Example 184A and the procedure described in Example 4C the desired compound was obtained.
MS (DCI) m/z 333 (M+H)+;
~ H NMR (300 MHz, DMSO) 8 10.76 (S, 1 H), 9.51 (S, 2H), 9.14 (S, 2H), 8.74 {S, 1 H), 3U 8.56 (S, I H), 8.33 (D, I H, J=8.8 Hz), 8.26 (D, 1 H, J=8.8 HZ Hz}, 8.16 (DD, 1 H, J=8.46, 1. I I Hz), 7.91 (M, 6H), 7.31 (S, 1 H};
Anal. calc'd for C2pH~7F3N404~I.5 H20: C, 53.28; H, 4.26; N, 11.83. Found: C, 53.47; H, 3.86; N, 11.96.

SUBSTITUTE SHEET (RULE 26) Exam Ip a 185 methvl2-II6-(aminoiminomethyll-2-na ht~h_alenylloxvlacetate mono(trifluoroacetate)(saltl Example 185A
7-methoxy-2-cyanonaphthalene, (2.79 g, 5.23 mmol) and tetrabutylammonium iodide ( 17 mg, 0.157 mmol) were combined in a mixture of benzene (35 mL) and cyclohexanes ( 17.5 mL). The resulting solution was added to a rapidly stirring, cooled (ice/water) suspension of aluminum triiodide (6.21 g, 15.23 mmol) in a mixture of benzene (35 mL) and cyclohexanes ( 17.5 mL) under an inert atmosphere. After the addition, the resulting suspension was heated at reflux for 2.5 hours. The heating was removed and after cooling to near room temperature, the reaction mixture was cooled in an ice bath and quenched by the addition of water (100 mL). The resulting mixture was further diluted with 2 M aqueous sodium thiosulfate solution (50 mL) and extracted with ethyl acetate (3 X 80 mL). The combined organic layers were dried and evaporated. The resulting solid was dissolved in a minimum of hot ethyl acetate, diluted hot ~ 5 with hexanes to the cloud point and placed in a refrigerator for 2 hours.
The desired compound was collected by filtration, ( 1.99 g, 77%).
MS (DCI (NH3)) m/z 187 (M+NI-I4)+.
xam lep 1858 The resulting product from Example 185A (217 mg, 1.283 mmol) was combined with cesium carbonate (460 mg, 1.411 mmol) and tetrabuthylammonium iodide (catalytic) in DMF (7 mL). To this was added t-butyl bromoacetate ( 193 ~tL, 1.283 mmol) and the resulting mixture was stirred 2 hours under an inert atmosphere. The reaction mixture was diluted with water ( 100 mL) and extracted with ethyl acetate (2 X 50 mL). The combined organic layers were dried and evaporated. The residue was purified by column chromatography to yield the desired compound as an oil (332 mg, 91 %):
MS (DCI (NH3)) m/z 284 (M+H) +, 301 (M+NH4)+.
Examnfe 185C
3o methyl 2-f16-(aminoiminomethyl)-2-na thalenylloxvlacerate mono(trifluoroacetatel( alt) The product from Example 1858 (323 mg, 1.140 mmol) was dissolved in anhydrous methanol (32 mL) under an inert atmosphere and cooled to 0 °C.
Anhydrous hydrogen chloride was bubbled into the solution until it became saturated. The reaction was stirred for 15 minutes at 0 °C and saturated again with anhydrous hydrogen chloride. After stirring for an additional 20 SUBSTITUTE SHEET (RULE 26) minutes at 0 °C the solution was saturated one final time with anhydrous hydrogen chloride and stirred 18 hours while warming to room temperature. The reaction was evaporated to a solid and dried under high vacuum for 2 hours. The solid was slurried in methanol (64 mL), ammonium acetate (220 mg, 2.850 mmol) was added, and the mixture was heated at reflux 2 hours. The reaction was evaporated and purified by reverse phase chromatography to give the desired compound (265 mg, 90%).
MS (DCI (NH3)) m/z 259 (M+H)+;
IH NMR (300 MHz, DMSO-d6) 8 3.735 (s, 3H), 4.995 (s, 2H), 7.430 (dd, 1H), 7.458 (s, 1 H}, 7.669 (dd, 1 H), 8.025 (d, 1 H}, 8.095 (d, 1 H), 8.325 (d, 1 H), 9.090 (br s, 1 H), 9.410 l0 (br s, 1 H;
Anal. calc'd for C14H~4N203~ (C2H02F3) 1.05: C, 51.16; H, 4.01; N, 7.41.
Found: C, 51.35; H, 3.98; N, 7.48.
Exam lie 1 R6 6-laminoiminomethyl)-N-(2-thiazolvl)-2-naphthalenecarboxamide monohydrochloride Example 186A
The above product was prepared in the manner of Example 8A using 2-aminothiazole.
MS (APCI) m/z (M+H)+ 280.

Example 186B
6-(aminoiminomethvl)-N-(2-thiazolvl)-2-nanhthalenecarboxamide monohvdrochloride The above was prepared from Example 1B.
MS (APCI) m/z (M+H)+ 297;
IH-NMR (3()0 MHz, DMSO-d6) 8 12.88 (s, IH), 9.59 (s, 2H), 9.30 (s, 2H), 8.87 (s, IH), 8.59 (s, 1 H), 8.32-8.22 (m, 4H), 7.93 (dd, J=1.8, 8.4 Hz, 1 H), 7.61 (d, J=3.3 Hz, ! H), 7.33 (d, J=3.3 Hz, IH);
Anal. calc'd for C~5H~3N40C1S 2/5 HC1: C, 52.03; H, 3.89; N, 16.18. Found: C, 52.01; H, 3.88; N, 16.12.
Example 187 6-(aminoiminomethvl)-N-f6-methoxy-3-wndin lv )-2-na~hthalenecarboxamide monohydrochloride SUBSTITUTE SHEET (RULE 26) Ex~arr ple 187A
The above product was prepared in the manner of Example 8A using 5-amino-2-methoxypyridine.
MS (APCI) m/z (M+H)+ 304.
Example 187B
6-(aminoiminomethyll-N-(6-methoxv-3-pyridin lv )-2-nanhthalenecarboxamide, monollydrochloride The above was prepared as described Example I B (144D).
1U MS (CI) m/z (M+H)+ 321;
1H-NMR (300 MHz, DMSO-d6) 8 10.71 (s, 1H), 9/60 (s, 2H), 9.41 (s, 2H), 8.76 (s, 1H), 8.60 (s, 2H), 8.30 (d, J=9, IH), 8.25-8.12 (m, 4H), 7.93 (dd, J=1.8, 8.7 Hz, 1H), 6.89 (d, J=9.0 Hz, I H), 3.87 (s, 3H);
Anal. calc'd for C2UH1~N404F3 1/2 TFA: C, 51.47; H, 3.60; N, 11.45. Found: C, 51.39; H, a 3.88; N, 11.65.
Example I88 6-(aminoiminomethyl)-N-( 1. 3-benzodioxol-5-yl)-2-naphthalenecarboxamide mono(trifluoroacetate)(sa~~

Example 188A
The above product was prepared in the manner of Example 8A using 3, 4-methylenedioxyaniline.
MS (APCI) m/z (M+H)+ 317.

Example 188B
The above was prepared as described Example 1 B.
MS (CI) m/z (M+H)+ 334;
1 H-NMR (300 MHz, DMSO-d~,) 8 9.70 (s, 1 H), 8.20 (s, 2H), 9.96 (s, I H), 7.81-87.63 (m, 3U 3H), 7.31 (dd, J=1.8> 8.4 Hz, IH), 7.11 (d, J=4.2 Hz, 1H), 6.91 (dd, J=4.5, 10.8 Hz), 6.4 (d, J=8.4 Hz, 1 H), 5.59 (s, 2H);
Anal. caIc'd for C21H1~N303F3 3/5 TFA: C, 55.44; H, 3.48; N, 8.77. Found: C, 55.44; H, 3.52; N, 8.85.

SUBSTITUTE SHEET (RULE 26) Exam I~e 1 H9 6-(aminoiminomethyl)-N-( 1. 2. 3. 4-tetrahydro-2. 4-dioxo5-Ryrimidinvl) 2-na>?hthalenecarboxamide. monohydrochloride Example 189A
The above product was prepared in the manner of Example 8A using 5-aminouracil.
MS (APCI) m/z (M-H)+ 305.
Example 189B
l0 ~~aminoiminomethyl)-N-(I 2 3 4-tetrahvdro-2 4-dioxo -pyrimidin, 2-nat~hthalenecarboxamide, monohydrochloride The above was prepared as described in Example 1 B.
MS (CI) m/z (M+H)+ 324;
~ H-NMR (300 MHz, DMSO-d6) 8 1 1.50 (s, 1 H), 10.90 (m, 1 H), 9.53 (s, 3H), 9.21 (s, 2H), ~5 8.70 (s, IH), 8.55 (s, 1H), 8.33 (d, J=8.4 Hz, 1H), 8.20 (d, J=8.7 Hz, 1H), 8.13-8.09 (m, 2H), 8.00 (s. 1 H), 7.88 (dd, J=I .8, 8.4 Hz, 1 H);
Anal. calc'd for C16H14N5~3C1 2/5 HC1: C, 51.49; H, 3.88; N, 18.76. Found: C, SI.87; H, 4.01; N, 17.68.
2U Example 190 ~aminoiminomethyl)-N-(3 5-difluor~henyl)-2-naphthalenecarboxamide mono(trifluoroacetatel(salt) Exam~ale 190A
25 The above product was prepared in the manner of Example 8A using 3, 5-difluoroaniline.
MS (APCI) m/z (M-H)+ 307.
Example 190B
3U 6-(aminoiminomethyl)-N-(3 5-difluoro h~envll-2-naphthalenecarboxamide monoltrifluoroacetatel~salt) The above was prepared as described in Example 1 B.
MS (CI) m/z (M+H)+ 326;

SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCTIUS98/15386 IH-NMR (300 MHz, DMSO-d6) 8 10.93 (s, 1H), 9.53 (s, 2H), 9.34 (s, 2H), 8.71 (s, 1H), 8.58 (s, 1 H), 8.33 (d, J=8.4 Hz, 1 H), 8.26 (d, J=8.7 Hz, 1 H), 8.14 (m, 1 H), 7.92 (dd, J=0.9, 8.1 Hz, 1 H), 7.61 (d, J=7.8 Hz, 2H}, 7.04-6.97 (m, 1 H);
Anal. calc'd for C2pH14N3O2F5 2/5 TFA: C, 54.92; H, 3.21; N, 9.42. Found: C, 54.96; H, 3.36; N, 9.37.
Example I91 6-(aminoiminomethvl)-N-(1H-pvrazol-3- 1)-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) Example 191 A
The above product was prepared in the manner of Example 8A using 3-aminopyrazole.
MS (APCI) m/z (M+H)+ 263.
Example 191 B
6-(aminoiminomethvll-N-( I H-pvrazol-3-vl)-2-naphthalenecarboxamide mono(trifluoroacetate)f salt) The above was prepared as desribed in Example 1 B.
MS (CI) m/z (M+H)+ 280;
IH-NMR (300 MHz, DMSO-d6) 8 I 1.13 (s, 1H), 9.55 (s, 2H), 9.37 (s, 2H), 8.75 (s, 1H), 8.55 (s, 1H), 8.23 (d, J=8.4 Hz, 1H), 8.12 (s, 2H), 7.90 (d, J=8.4 Hz, 1H)>
7.70 (s, IH), 6.69 (s, 1 H);
Anal. calc'd for C17H14N503F3 7/10 TFA: C, 46.53; H, 3.12; N, 14.70. Found: C, 46.47;
H, 3.16; N, 14.85.
Example 192 6-(aminoiminomethvl)-N-(5-methyl-'3-isoxazolyll)-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) p Example 192A
The above product was prepared in the manner of Example 8A using 3-amino-5-methylisoxazole.
MS (APCI) m/z (M+H}+ 278.

SUBSTITUTE SHEET (RULE 26) Example 192B
6-laminoiminomethyi)-N-(5-methyl-3-isoxazol r~lll-2-nanhthalenecarboxamide mQno(trifluoroacetate)( alt) The above was prepared as described in Example 1 B.
s MS (CI) m/z (M+H)+ 295;
1 H-NMR (300 MHz, d6-DMSO) 8 I 1.62 (s, 1 H), 9.52 (s, 2H), 9.33 (s, 2H), 8.78 (s, 1 H), 8.55 (dd, 1H), 8.31-8.16 (m, 3H), 7.90 (dd, 1H), 6.81 {s, 1H), 2.44 (s, 3H) Anal. calc'd for CIgH15N404F3: C, 52.95; H, 3.70; N, 13.72. Found: C, 52.73;
H, 3.64; N, 13.24.
t0 Example 193 6-(aminoiminomethvl)-N-(nvrazinyl)-2-naphthalenecarboxamide mono(trifluoroacetate)(~~lt) Example 193A
15 The above product was prepared in the manner of Example 8A using 2-aminopyrazine.
MS (APCI) m/z (M-H)+ 275.
Example 193B
6-(aminoiminomethvl)-N-(pyrazinyl)-2-nanhthalenecarboxamide mono(trifluoroacetate)(salt) z0 The above was prepared as described in Example 1 B.
MS (CI) m/z (M+H)+ 292;
~ H-NMR (300 MHz, d~,-DMSO) b 11.41 (s, 1 H), 9.52 (s, 2H), 9.49 (s, 1 H), 9.27 (s, 2H), 8.83 (s, 1 H), 8.56 (s, 1 H), 8.53-8.46 (m, 2H), 8.30 (d, 1 H), 8.23 (s, 2H), 7.90 (dd, 1 H);
Anal. calc'd for C~~H~4NS03F3: C, 49.36; H, 3.16; N, 15.15 1/2 TFA. Found: C, 49.53; H, 25 3.22; N, i 4.87.
Exam-ple 194 6-(aminoiminomethvl)-N-(6-meth~pyridin 1)-2-naphthalenecarboxamide monoltrifluoroacetate)( alt) Example 194A
The above product was prepared in the manner of Example 8A using 2-amino-6-methylpyridine.
MS (APCI) m/z (M+H)+ 288.

SUBSTITUTE SHEET (RUtE 2fi) Example 194B
6-(aminoiminomethvl)-N-l6-methyl-2-p 'dinvl)-2-naDhthalenecarboxamide mono(trifluoroacetate)(salt) The above was prepared as described in Example 1 B.
MS (C1) m/z (M+H)+ 305:
~H-NMR (300 MHz, d6-DMSO) 8 11.02 (s, 1H), 9.53 (s, 2H), 9.37 (s, 2H), 8.80 (s, 1H), 8.55 (s, 1H)> 8.29 (d, 1H), 8.20 (s, 2H), 8.07 (d, 1H), 7.89 (d, 1H)> 7.78 (t, 1H), 7.08 (d, 1 H), 2.48 (s, 3H);
t0 Anal. calc'd for C20H17N403F3~ C, 48.74; H> 3.33: N, 10.20 715 TFA. Found:
C, 48.74; H, 3.59; N, 10. I 1.
Example 195 6-(aminoiminomethvl)-N-(3. 4, 5-trimethoxvphenyI)-2-n~~hthalenecarboxamide monohydrochloride Example 195A
The above product was prepared in the manner of Example 8A using 3> 4, 5-trimethoxyaniline.
2o MS (APCI) m/z (M+H)+ 363.
Example 195B
6-(aminoiminomethvl)-N-(3. 4. 5-trimethoxvphenvl)-2-n~phthalenecarboxamide mono~drochloride 25 The above was prepared as described in Example 1 B.
MS {CI) m/z (M+H)+ 380;
~ H-NMR (300 MHz, d~-DMSO) b 10.54 (s, 1 H), 9.61 (s, 2H), 9.34 (s, 2H), 8.72 (s, 1 H), 8.59 (s, 1H), 8.33-8.15 (m, 3H), 7.91 {dd, 1H), 7.30 (s, 2H), 3.80 (s, 9H) Anai. calc'd for C21H22N304C1 63/10 HCI: C, 39.09; H, 4.42; N, 6.SI. Found: C, 38.94; H, 30 4.60: N, 7.61.
Exam lie 196 6-(aminoiminomethvl)-N-( -methyl-2-p 'din~rl)-2-nanhthalenecarboxamide bis~trifluoroacetateO(salt) SUBSTITUTE SHEET (RULE 26) Example 196A
Using the procedure described for Example I84A and substituting 2-amino-3-picolene for 4-aminobenzamide, the desired compound was obtained.
MS (DCI) m/z 288 (M+H)+.
Example 196B
6-laminoiminomethvll-N-l3-methyl-2-nvridi ~1)-2-nanhthalenecarboxamide bisftrifluoroacetate)(salt~
Using the procedure described in Example 1B and the product obtained in Example 196A, the desired compound was obtained.
MS (DCI) m/z 305 (M+H)+;
~ H NMR (300 MHz, DMSO) 8 10.85 (s, 1 H), 9.52 (s, 2H), 9.22 (s, 2H), 8.76 (s, 1 H), 8.56 (s. I H), 8.35 (dd, 1 H, J=4.41, 1.10), 8.32 (d, 1 H, J=8.80), 8.22 (m, 2H), 7.90 (dd, 1 H, J=8.83, 1.84), 7.80 (dd, I H, J=7.73, 1.11 ), 7.3 I (dd, 1 H, J=7.72, 4.78), 2.26 (s, 1 H);
Anal. calc'd for C22H1gF6N403~0.75 H20: C. 48.40; H, 3.60; N, 10.26. Found: C, 48.81;
H, 3.66; N, 10.43.
Exam l 6-f aminoiminomethyll-N-(5-bromo-2-thiazolyll)-2-nanhthalenecarboxamide mono(trif?uoroacetate)(salt~
Example 197A
Using the procedure described for Example 184A and substituting 2-amino-5-~5 bromothiazole for 4-aminobenzamide, the desired compound was obtained.
MS (DCI) m/z 358 (M+H)+.
Example 197B
6-faminoiminomethvll-N-(5-bromo-2-thiazolvll)-2-naphthalenecarboxamide 3o monoltrifluoroacetate)(salt~
Using the procedure described in Example 1B and the product obtained in Example 197A, the desired compound was obtained.
MS (ESI+) m/z 375 (M+H)+;

SUBSTITUTE SHEET (RULE 26) 1H NMR (300 MHz, DMSO) 8 10.85 (s, 1H), 9.55 (s, 2H), 9.24 (s, 2H), 8.87 (s, iH), 8.57 {d, I H, J=1.69), 8.31 (d, I H, J=8.47), 8.25 (d, 2H, J=1.01 ), 7.92 (dd, 1 H, J=8.48, 2.04), 7.71 {s, 1 H);
Anal. calc'd for C~~HI2BrF3SN403~ 1.25 H20~0.25 TFA: C. 38.90; H, 2.75; N, 10.37.
Found: C, 38.97; H, 3.24; N, 10.66.
Example 198 6-(aminoiminomethvl)-N-(5-methyl-2-pvridinvl)-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) to Example 198A
Using the procedure described for Example 184A and substituting 2-amino-5-picolene for 4-aminobenzamide, the desired compound was obtained.
MS (ESI+) m/z 288 (M+H)+.
Example 1988 6-(aminoiminomethvl)-N-(5-methyl-2-p 'dinyl~-2-naphthalenecarboxamide mo_no(trifluoroacetate)(salt) Using the procedure described in Example 1 B and the product obtained in Example 2U 198A, the desired compound was obtained.
MS (DCI) m/z 305 (M+H)+;
1 H NMR (300 MHz, DMSO) 8 1 I .0 l (s, 1 H), 9.50 (s, 2H), 9.16 {s, 2H), 8.79 (s, 1 H), 8.54 (s, 1 H), 8.30 (d, 1 H, J=9.19), 8.27 (d, I H, J=1.47), 8.20 (s. 2H), 8. I 5 (d, 1 H, J=8.83), 7.89 (dd. 1 H, J=8.46, 1.48), 7.72 (dd, I H, J=8.46, 1.84), 2.31 (s, 3H);
Anal. calc'd for C2pH17F3N403~0.25 H20~0.2 TFA: C, 54.98; H, 4.00; N, 12.57.
Found: C, 54.99; H, 3.59; N, 12.43.
Example 199 6-laminoiminomethvl)-N-(4-methyl-2-thiazolyl)-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) Example 199A
Using the procedure described for Example I84A and substituting 2-amino-5-methyl benzothiazoIe for 4-aminobenzamide, the desired compound was obtained.

SUBSTITUTE SHEET (RULE 26) MS (ESI-) m/z 293 (M+H)-.
Example 199B
6-(aminoiminomethvll-N-(4-methyl-2-thiazolvl)-2-naphthalenecarboxamide monoltrifluoroacetate)(salt) Using the procedure described in Example 1 B and the product obtained in Example I 99A, the desired compound was obtained.
MS (ESI+) m/z 31 I (M+H)+;
~ H NMR (300 MHz, DMSO) 8 9.51 (s, 2H), 9.25 (s, 2H), 8.86 (s, 1 H), 8.55 (s, 1 H), 8.30 {d, 1H, J=8.48), 8.25 (d, 1H, J=2.03), 7.91 (dd, 1H, J=8.48, I.70), 6.87 (s, 1H), 2.34 (s, 3H);
Anal. calc'd for CigH~5F3N4S03~0.5 TFA: C, 47.40; H, 3.25; N, I I.64. Found:
C, 47.90;
H, 3.36; N, 11.71.
Example 200 6-(aminoiminomethvl l-4-f 5-(ethylthio)-3-furanyll-N-phenyl-2-naphthalenecarboxamide monohydrochloride Example 200A
The desired compound was prepared from 2-trimethylsilyl-3-bromofuran and diethyldisulfide by the procedure of Example 154A.
MS (DCI/NH3) m/z 279, 281 (M+H)+.
Example 200B
A solution of the product from Example 200A (8.60 g, 30.8 mmol) in THF (20 mL) and a 1 M solution of TBAF (61.6 mL) was stirred for 24 hours. The reaction was condensed and chromatographed on Si02 using hexanes as eluent, to yield 3.32 g (52%) of 2-ethylthio-4-bromofuran. The desired compound was prepared from this material by the procedure of Example 57A.
MS (DCI/NH3) m/z 127 (M-B (OH)z)+.
Example 200C
The desired compound was prepared from the product from Example 200B and the product from Example 152C by the procedure of Example 57B.

SU9STITUTE SHEET (RULE 26) MS (DCI/NH3) m/z 416 (M+NH4)+.
E_xamnle 200D
6-faminoiminomethvl)-4-15-(ethvlthio)-3-furanyll-N-yhenyl-2-naphthalenecarboxamide monohvdrochloride The desired compound was prepared from Example 200C and the procedure of Example 144C.
MS (DCI/NH3j m/z 416 (M+H)+;
~ H NMR (300 MHz, DMSO-d6) 8 1.30 (t. 3H), 2.92 (q, 2H), 7.15 (t, 1 H), 7.34 (s, 1 H), t0 7.40 (t, 2H), 7.83 (d, 2H), 7.92 (dd, 1H), 8.20 (d, 1H), 8.40 (d, 1H), 8.47 (s, 1H), 8.60 (s, 1 H), 8.69 (s, 1 H), 9.21 (br s, 2H), 9.58 (br s, 2H), 10.61 (s, 1 H);
Anal. calc'd for C24H21N3S02~1.5 HCI: C, 61.31; H, 4.82; N, 8.94. Found: C, 61.39; H, 4.89; N, 9.03.
is Example 201 6-(aminoiminomethvl)-4-f S-(pronylthio)-3-furanyll-N-phe~l-2-naphthalenecarboxamide monohydrochloride Example 20I A
2o The desired compound was prepared from 2-trimethylsilyl-3-bromofuran and dipropyldisulfide by the procedure of Example 1S4A.
MS {DCI/NH3) m/z 293, 29S (M+H)+.
Example 201 B
?S The desired compound was prepared from the product from Example 201 A by the procedure of 1 S4B.
MS (DCl/NH3) m/z 432 (M+H)+.
Example 201 C
3o The desired compound was prepared from the product from Example 201B and the product from Example 1 S2C by the procedure of Example I S4C.
MS (DCI/NH~) m/z 430 (M+NH4)+.
Example 201 D

SUBSTITUTE SHEET (RULE 26) 6-laminoiminomethvl)-4-f5-l r~o~ylthio)-3-furan l~phen 1-y_ 2~naphthalenecarboxamide rt~onohvdrochloride The desired compound was prepared from Example 201C and the procedure of Example 144C.
MS (DCI/NH3) m/z 430 (M+H)+;
~H NMR {300 MHz, DMSO-d6) 8 I.O1 (t, 3H), 1.66 (qt, 2H), 2.89 (t, 2H), 7.15 (t, 1H), 7.34 (s, 1H), 7.40 (t, 2H), 7.84 (d, 2H), 7.92 (dd, 1H), 8.20 (d, 1H), 8.40 (d, IH), 8.47 (s, 1 H), 8.60 (s, 1H), 8.69 (s, 1 H), 9.22 (br s, 2H), 9.58 (br s, 2H), 10.61 (s, 1 H);
Anal. calc'd for C25H23N3S02~ I .25 HC1: C, 63.20; H, 5. I4; N, 8.84. Found:
C, 63.24; H, to 5.16; N, 8.93.
Example 202 6-laminoiminomethyl)-N-l6-quinolinvl)-2-naphthalenecarboxamide bis(trifluoroacetate)(salt) (5 Example 202A
To a solution of the acid chloride, Example 8B, (331 mg, 1.5 mmol) in THF ( 15 mL), at room temperature, was added propylene oxide ( 10 mL), DMAP (5 mg), a drop of triethylamine and finally 6-aminoquinoline (288 mg, 2.0 mmol). After 4 hours at room 2O temperature, added ethyl acetate ( 10 mL) and ether (20 mL) and filtered the off-white solid product. Yield 357 mg (7290).
MS (DCI/NH3) m/z 324 (M+H)+.
Examlale 202B
25 6-laminoiminomethvl)-N-(6-quinoiinvl)-2-n~phthalenecarboxamide bis(trifl uoroacetate)lsalt) The desired compound was prepared as described in Example 1 B.
MS (ESI+) m/z 341 (M+H)+, (ESI-) 339 (M-I)-;
~ H NMR (300 MHz, DMSO-d6) 8 10.98 (s, 1 H), 9.53 (s, 2H), 9.25 (s, 2H), $.93-8.91 (m, 30 1 H), 8.77 (s, 1 H), 8.67 (d, J= I .BHz, 1 H), 8.58 (s, 1 H), 8.53 (d, J=8.SHz, 1 H), 8.37-8.09 (m, SH), 7.93 (dd, J 1=B.SHz, J2=I .BHz, 1 H), 7.65-7.62 (m, 1 H);
Anal. calc'd for C=,H,6N40~2TFA: C, 52.83; H, 3.19; N, 9.86. Found: C, 52.62;
H, 2.94; N, 9.74.

SUBSTITUTE SHEET (RULE 26) Exam Ip a 203 6-(aminoiminomethyl)-N-( 1 H-indazol-6-vl)-2-n~phthalenecarboxamide bis(trifluoraacetat s It S Example 203A
The desired compound was prepared as described for Example 202A but substituting 6-aminoquinoline for 6-aminoindazvle to provide 285 mg of the desired compound.
MS: ESI+: 313 (M+1); ESI-311 (M-I).
Example 203B
6-(aminoiminomethvl)-N-(1 H-indazol-6-yIl-2-nanhthalenecarboxamide bis(trifluoroasetate)(taltl To a suspension of the ammonium chloride ( 140 mg, 2.6 mmol) in Toluene (2 mL) at 0°C was slowly added a solution of 2 N trimethylaluminium in toluene (871~tL, 1.74 mmol).
is After 5 minute the reaction mixture was allowed to warm to room temperature for 3U minutes.
To the solution of the aluminium reagent at room temperature was added the nitrite, Example 203A from section (a) and the reaction mixture was heated to 100°C for 48 hours. The reaction mixture was cooled down then was poured into a suspension of silica in chloroform and stirred for an hour. The silica was filtered then washed with methanol. The solvent was concentrated zo and purified by medium pressure liquid chromatography on a 30 cm x 2 cm C-I8 column (40 micron, J.T Baker) with UV detection at 250 nM with solvent mixtures in a gradient ranging from 90%A (0.1% aq TFA)/IU%B (methanol) to 10%A/90%B over 160 minutes at a flow rate of 5 mL/min (fractions were collected every 2 minutes for 100 min, to provide 42 mg of the desired compound.
25 MS (ESI+) m/z 330 (M+H)+, (ESI-) 328 (M-1)-;
~H NMR (300 MHz, DMSO-d6) 8 10.65 (s, IH), 9.47 (m, 4H), 8.65 (s, 2H), 8.50 (s, 2H), 8.25-8.23 (m, 2H), 8.17-8.10 (m, 2H), 7.94 (s, 1H), 7.86-7.84 (dd, J1=8.8Hz, J2=l.6Hz, 1 H), 7.66 (d, J=8.SHz, I H), 7.37 (d, J=8.4Hz, 1 H);
Anal. calc'd for C19H15Ng 0~2 TFA: C, 49.56; H, 3.07; N, 12.56. Found: C, 49.68; H, ~a 3.10; N, 12.47.
Example 204 6-laminoiminomethvl )-N-( I H-indazol-5-yI)-2-naphthalenecarboxamide bisltrifluoroacetat .ll.calt) SUBSTITUTE SHEET (RULE 26) Example 204A
The desired compound was prepared as described for Example 202A but substituting 6-aminoquinoline for 5-aminoindazole to provide 362 mg of the desired compound.
MS: ESI+: 313 (M+1); ESI-311 (M-I).
Example 204B
6-(aminoiminomethvll-N-l I H-indazol- ;yl -2-na hthalenecarboxamide bisltrifluoroacetate)(salt), lU The desired compound was prepared as described for Example 203B to provide 55 mg of the desired compound.
MS (ESI+) m/z 330 (M+H)+, (ESI-) 328 (M-I)-;
1 H NMR (300 MHz, DMSO-d~,) ~ 13.06 (s, I H), 10.58 (s, 1 H), 9.51 (s, 2H), 9.15 (s, 2H), 8.71 (d, j=l.9Hz, 1H), 8.56 (d, j=l.9Hz, 1H), 8.34-8.17 (m, 4H), 8.10 (s, IH), 7.90 (dd, ~5 J 1=B.SHz, J2=1.7Hz, 1 H), 7.63 {dd, J 1=8.9Hz, J2=I.7Hz, 1H), 7.56 (d, J=8.8Hz, 1 H);
Anal. calc'd for CIyHiSNS O~TFA~ 1.75 H20: C, 53.11; H, 4.14; N, 14.75. Found:
C, 53.20; H. 3.99; N, 14.42.
Example 205 20 6-laminoiminomethyt)-N-l I H-indol-5-vll-~-nawhthalenecarboxamide mono(trifluoroacetate)( altl Example 205A
The desired compound was prepared as described for Example 202A but substituting 6-25 aminoquinoline for 6-aminoindole to provide 744 mg of the desired compound.
MS: (ESI)+: 329 (M+1)+ and (ESI)-: 327 (M-1)-.
Example 205B
fi--(aminoiminomethvl)-N-l 1 H-indol- -yl~nayhthalenecarboxamide monoltrifluoroacetate)(saltl The desired compound was prepared as described for Example 203B to provide 90 mg of the desired compound.
MS (ES1*) m/z 329 (M+H)+, (ESI-) 327 (M-1)-;

SU6STiTUTE SHEET (RULE 26) ~H NMR (300 MHz, DMSO-d6) 8 11.09 (s, 1H), 10.40 (s, 1H), 9.5I (s, 2H), 9.15 (s, 2H), 8.71 (s, 1H), 8.55 (s, IH), 8.32 (d, J=8.4Hz, 1H}, 8.26-8.17 (m, ZH), 8.05 (d, J=2.6Hz, 1 H), 7.90 (dd, J 1=8.4Hz, J2=1.BHz, 1 H), 7.46-7.35 (m, 3H), 6.45-6.43 (m, 1 H);
Anal. calc'd for C2pH16N4 O~TFA: C, 59.73; H, 3.87; N, 12.66. Found: C, 59.27;
H, 4.17;
N, 12.74.
Example 206 7-f2-(4-momholinvl)ethoxvl-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) 1 p Example 206A
The nitrite was prepared as described in Example 119A using 2-chloroethylmorpholine.
MS (DCI (NH3)j m/z 283 (M+H) +.
Example 206B
7-f2-(4-momholinvl)ethoxvl-2-naphthalenecarboximidamide bis(trifluoroacetate)(salt) The desired compound was prepared as described in Example 1 19B, as an off-white solid (50°lo yield).
MS (DCI (NH3)) m/z 300 (M+H)+;
~H NMR (300 MHz, DMSO-d6j 8 3.500 (br m, 4H), 3.700 (br m, 2H), 3.990 (br m, 4H), 2p 4.490 (br m, 2H), 7.435 (dd, 1 H), 7.530 (d, 1 H), 7.680 (dd, 1 H), 8.035 (d, 1 H), 8.100 (d, 1 H), 8.345 (d 1 H), 9.165 (br s, 2H), 9.420 (br s, 2H);
Anal. calc'd for CpH21N302~ (C2H02F3) 2.15: C, 46.98; H, 4.29; N, 7.72. Found:
C, 47.00;
H, 4.32; N, 7.77.
'S Example 207 6-(aminoiminomethyl)-N-phen 1-v 4-(2-pyrrolidinyl)-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) Exam,~le 207A
3p The desired compound was prepared from the product from Example 152A, by the procedure of Example 68A.
MS (DCI/NH3) m/z 281 (M+H)+.
Example 207B

SUBSTITUTE SHEET (RULE 26) The desired compound was prepared from the product from Example 207A by the procedure of Example 152B.
MS (DCI/NH3) m/z 267 (M+H)+.
Example 207C
A solution of the product from Example 207B (220 mg, 0.826 mmol), diisopropylethyl amine (0.288 mL, 1.65 mmol), and O- (7-azabenzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate (314 mg, 0.826 mmoI) in DMF ( 10 mL) was stirred for 30 minutes at 0°C. Aniline (0.083 mL, 0.909 mmol) was added, and the reaction was t0 stirred at room temperature for 4 hours. The reaction was poured into saturated aqueous Na2C03 solution, and extracted with 3x ethyl acetate. The combined extracts were washed with water and brine, dried over Na2S04, and condensed. The crude material was recrystallized from ethanol/hexanes to yield 212 mg (75%) of the desired compound.
MS (DCI/NH3) m/z 342 (M+H)+.
iS
Exam In a 207D
6-(aminoiminomethvl)-N-phenyl-4-!2-pyrrolidin I -2-n ~~phthalenecarboxamid~, monoltrifluoroacetatel( altl The desired compound was prepared from Example 207C and the procedure of Example 20 t B .
MS (DCI/NH3) m/z 359 (M+H)+;
IH NMR (300 MHz, DMSO-d~,) 8 2.02 (t, 4H), 3.55 (t, 4H), 7.13 (t, IH), 7.38 (t, 2H), 7.41 (s, 1 H), 7.80 (m, 3H), 8.08 (s, I H), 8. I 8 (d, 1 H), 8.67 (s, I H), 9.10 (br s. 2H), 9.43 (br s, 2H), 10.41 (br s, IH);
25 Anal. calc'd for C22H22N40~ 1.0 C2HF302: C, 61.01; H, 4.91; N, I 1.86.
Found: C, 60.47;
H, 5.36; N, 7.39.
Example 208 6-faminoiminomethvl)-N-l5-Ryrimidinvll-2-nanhthalenecarboxamide -t~l monoltrifluoroacetate)( alt?
Example 208A
The above product was prepared in the manner of Example 8A using 5-aminopyrimidne.

SUBSTITUTE SHEET (RULE 26) MS (APCI) m/z (M+H)+ 275.
~xamnle 208B
6-(aminoiminomethyI)-N-(5-pvrimidinyl~-~-naphthalenecarboxamide mono(trifluoroacetate)(sal 7 The above was prepared as described in Example 1B.
MS (CI) m/z (M+H}+ 292;
~H-NMR (300 MHz, DMSO-d6) 8 10.99 (s, 1H), 9.52 (s, 2H), 9.27 (s, ZH), 9.24 (s, 2H), 8.98 (s, IH), 8.76 (s, 1H), 8.58 (s, IH), 8.36-8.18 (m, 3H), 7.92 (dd> J=1.5, 8.4 Hz, 1H);
Anal. calc'd for C~gH14N503F3 7/10 TFA: C, 47.97; H, 3.05; N, 14.40. Found: C, 47.78;
H, 3.05; N, 14.67.
Exam In a 2~9 6-laminoiminomethyl -N-('~-pyri a~inyl)-2-nanhthalenecarboxamide 5 mono(trifluoroacetatel(salt) Example 209A
3-Amino-6-chloropyridazine ( I.OS g, 8.2 mmol) was dissolved in 10 mL methanol with 2 mL ammonia/methanol. Palladium/carbon (200 mg, 10°~0) was added and stirred under 1 atm hydrogen for 4 hours. The reaction was filtered, concentrated, and used without further purification.
MS (CI) m/z (M+H)+ 96.
Example 209B
The above product was prepared in the manner of Example 12 using the product from Example 209A.
MS (APCI) m/z (M+H)+ 275.
Example 2090 6-(aminoiminomethyl)-N-(3-p ridazinyll-2-nanhthalenerarboxarnid~, mono(trifluoroacetatP)(~,I ~, The above was prepared from Example 209B as described in Example I B.
MS (CI) m/z (M+H)+ 292;
-19b-SUBSTITUTE SHEET (RULE 26) tH-NMR (300 MHz, d6-DMSO) 8 11.72 (s, iH}, 9.51 (s, 2H), 9.22 (s, 2H), 9.06 (m, IH), 8.86 (s> IH), 8.56 (s, IH), 8.45 (d, 1H), 8.31 {d, IH)> 8.23 (s, 2H), 7.90 (dd, 1H), 7.78 (dd> I H) Anal. calc'd for C1gH14N503F3 1/2 TFA: C, 49.29; H, 3.16; N, 14.73. Found: C, 49.56; H, 3.23; N, 14.73.
Example 210 6-(aminoiminomethyl)-N-(5-bromo-2-p"vridin I -2-naphthalenecarboxamid~
mono(trifluoroacetate)(salt) Example 210A
Using the product obtained in Example 8E, 2-amino-5-bromopyridine, and the procedure described for Example 8G the desired compound was obtained.
MS (APCI+) tn/z 352 (M+H)+.

Example 210B
6-(aminoiminomethvl)-N-(5-bromo-2-pyridin 11-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) Using the procedure described in Example 1B and the product obtained in Example 20 210A, the desired compound was obtained.
MS (DCI) m/z 369 (M+H)+;
tH NMR (300 MHz, DMSO) 8 I 1.30 (s, 1H), 9.51 (s, 2H), 9.17 (s, 2H), 8.80 (s, 1H), 8.57 (d, 1 H, J=2.57), 8.55 (s, 1 H), 8.31 (d, 1 H, J=8.45), 8.26 (d, 1 H, J=8.82), 8.19-8.24 (m, 2H, ), 8.14 (dd, I H, J=2.57, 9.19), 7.90 (dd, 1 H, J=1.83, 8.82;
25 Anal. calc'd for C19Hj4BrF~N403: C, 47.22; H, 2.92; N, 1 1.59. Found: C, 47.60; H, 3.01;
N, 11.30.
Example 211 6-(aminoiminomethvl)-N-13-(I-methvlethoxy)phen I -2-naphthalenecarboxamide 3o mono(trifluoroacetatel(salt) Example 21 I A
The above product was prepared in the manner of Example 12 using 3-isopropoxyaniline.

SUBSTITUTE SHEET (RUtE 26) MS (APCI) m/z (M+H)+ 331.
Example 211 B
6-(aminoiminomethvl)-N-f3-l I-methylethoxy)phenyll-2-na",phthalenecarboxamide mono(trifluoroacetatel(salt~
The above was prepared from Example 21 IA using method 1B.
MS (CI) m/z (M+H)+ 348;
t H-NMR (300 MHz, d6-DMSO) 8 10.50 (s, 1 H), 9.50 (s, 2H), 9.22 (s, 2H), 8.67 (s, 1 H), 8.56 (s, 1 H), 8.3I (d, 1 H), 8.25-8. I 3 (m, 2H), 7.90 (dd, I H), 7.51 (m, 1 H), 7.36 (m, I H), 7.26 (t, 1 H), 6.68 (dd, I H), 4.59 (m, 1 H), 1.30 (d, 6H) Anal. calc'd for C23H2~N304F3 1/5 TFA: C, 57.96; H, 4.61; N, 8.66. Found: C, 57.99; H, 4.90; N, 8.68.
Example 212 t5 2-IT6-(aminoiminome~hvl)-2-na hthalen~lo~lacetic acid mono(trifluoroacetate)(salt) The product from Example 185C ( 140 mg, 0.542 mmoi) was dissolved in methanol ( 1 1 mL). To this was added a solution of lithium hydroxide (68.2 mg, 1.626 mmol) in water (3 mL) and the resulting mixture was stirred at room temperature under an inert atmosphere for 18 2o hours. The reaction was evaporated and the residue purified by reverse phase chromatography to yield the desired compound (102 mg, 52%).
MS {DCI (NH3)) m/z 245 (M+H)+;
t H NMR (300 MHz, DMSO-d6) b 4.875 (s, 2H), 7.420 (s, 1 H), 7.435 (dd, i H), 7.660 (dd, 1 H), 8.015 (d, I H), 8.100 (d, 1 H), 8.340 (d, 1 H), 9.125 (br s, 1 H), 9.420 (br s, 1 H;
?S Anal. calc'd for C13H~2N203~ (C2H02F3)t.3(t: C. 47.74; H, 3.42; N, 7.14.
Found: C, 47.93;
H, 3.36; N, 7.I7.
Example 213 methyl 4-f6-(aminoiminomethyl~2-na~hthalenyl loxvlmethvilbenzoate 3(~ monoltrifluoroacetate)(salt) Example 2I A
The resulting product from Example 185A was treated with methyl 4-(bromomethyl)benzoate in an analogous manner as described in Example 119B.

SUBSTITUTE SHEET (RULE 26) MS (DCI (NH3)) m/z 335 (M+NH4)+.
Example 213B
methyl4-16-(aminoiminometh l~aphthalen llox l~hyllbenzoate mono(trifluoroacetate)(salt~
The resulting product from Example 213A (250 mg, 0.78$ mmol) was treated in an analogous manner as described in Example 119C to yield the desired compound ( 130 mg, 79%).
MS (DCI (NH3)) m/z 335 (M+H) +;
~u ~H NMR (300 MHz, DMSO-d6) 8 3.870 (s, 3H), 5.400 (s, 2H), 7.500 (dd, 1H), 7.540 (d, 1 H), 7.619 (dd, 1 H), 7.620 (d, 2H), 8.025 (d, 2H), 8.026 (d, I H), 8.090 (d, 1 H), 8.410 (d, 1 H), 9.260 (v br s, 3H);
Anal. calc'd for C~4H14N~03~C2H02F3~H20 0.70: C, 57.32; H, 4.46; N, 6.08.
Found: C, 57.33; H, 4.70; N, 5.95.
l5 Example 214 6-(aminoiminomethvl)-N-( 1 H-imidazolyl)-2-naphthalenecarboxamide bis(trifluoroacetate)(salt) 2u Example 214A
Using the product obtained in Example 8E, 2-aminoimidazole, and the procedure described for Example 8G the desired compound was obtained.
MS (ESI-) m/z 261 (M+H)-.
25 Example 2I4B
Using the procedure described in Example 1 B and the product obtained in Example 214A, the desired compound was obtained.
MS (ESI+) m/z 280 (M+H)+;
~ H NMR (300 MHz, DMSO) 8 9.50 (s, 2H), 9.16 (s, 2H), 8.78 {s, I H), 8.53 (s, 1 H), 8.26-30 8.31 (m, 2H), 8.20 (d, 1H, J=8.46), 7.88 (dd, 1H, J=1.84, 8.83), 6.95 (s, 2H);
Anal. calc'd for C17H~4F3N503~0.2 TFA~H20: C, 48.14; H, 3.76; N, 16.13. Found:
C, 48.54; H, 3.40; N, 16.02.
Example 215 SUBSTITUTE SHEET (RULE 26) 6-12-f4-lhvdrox m~eth_yllphen_yll-1-cvclo~ropvll-2-naphthaleneca_rboximidamide monoltrifluoroacetate)l alt) Example I SA
The material prepared as described in Example 104 (210 mg, .52 mmol) is dissolved in THF (6 mL) and added dropwise to 10 mL diazomethane cooled to 0 °C then added Pd (OAc)2 (9.8 mg). Vigorous bubbling occurs for 5 minutes. the resulting black slurry is stirred 20 min, filtered and solvent removed under vacuum leaving 0. I g clear oil.
MS (DCI/NH3): m/z {M+NH4+): 316.
IU
Examvle 215B
6-f2-14-(hvdroxvmethvl)phen Iv 1-I-cyclopropyll-2-nanhthalenecarboximidamide monoltrifluoroacetate)(cal~
The desired compound is prepared as described in Example l, purified by reverse phase chromatography to give 19.9 mg of white solid.
MS (DCl/NH3) m/z (M+H)+ 316;
~H-NMR (300 MHz, DMSO-d6) b 9.41 (s, 2H), 9.16 (s, 2H), Ii.46 (s, lHj, 8.08 (d, 2H), H.03 (d, 1 H), 7.85 (s, 1 H), 7.75 (dd, 1 H), 7.58 (dd, 1 H), 7.3-7.1 (m, 4H), 4.49 (s, 2H), 2.38-2.48 (m, 2H), 1.61-1.70 (m, 2H);
2o Anal. calc'd for C23H21N202F3 I H20: C, 62.10; H, 4.80; N, 6.29. Found: C, 62.00; H, 4, 7s; N, 6.zs.
Exam lp a 216 N-(ethoxvcarbonvl)-6-l2-phenyl-1-cyclo rop I~a~phthalenecarboximidamide The sample described in Example 97 ( 130 mg, .45 mmolj is dissolved in DMF (3 mL) cooled to 0 °C. and treated with triethylarnine (0.01 mL) and ethyl chloroformate (0.05 mL).
The resulting solution is stirred three days at room temperature then diluted with 100 mL ethyl acetate washed with distilled water (20 mL), dried over anhydrous sodium sulfate, filtered and solvent removed under vacuum leaving a clear oil. The oil is purified by silica gel chromatography eluting with 2: 1 hexanes/ethyl acetate, lyophilized and the desired compound is isolated as a white powder (55 mg).
MS (DCI/NH3) m/z (M+H)+ 359;

SUBSTITUTE SHEET (RULE 26) WO 99!05096 PCTIUS98/15386 t H-NMR (300 MHz, DMSO-d6} b 9.21 (s, 2H), 8.46 (s, I H), 7.83 (d, 2H), 7.62 (s, I H), 7.58 (dd, 1H), 7.34 (dd, 1 H), 7.35-7.29 (m, 3H), 7.25-7.17 (m, 2H) 4.1 (q, 2H), 2.38-2.28 (m, 2H), 1.61 (t, 2H), I.25 (t, 3H);
Anal. calc'd for C23H22N2O2 C, 77.07; H, 6.19; N, 7.82. Found: C, 76.63; H, 6.05; N, 7.45.
Example 217 6-(aminoiminomethvl)-N-(2-methvl-6 guinolinyl)-2-naphthalenecarboxamide bis(trifluoroacetate)(salt) t0 The desired compound is prepared in a similar manner as described in Example 8E and 144C.
MS m/z: 355 (M+H)+
~ H NMR (DMSO, 300 MHz): 10.95 (s, 1 H}, 9.5 I (s, 2H), 9.14 (s, 2H), 8.75 (s, 1 H), 8.65 (s, 1H), 8.57 (s, 1H), 8.35 (dd, 1H, J1=J2=8.5 Hz), 8.28 (dd. 1H, Jl=J2=B.SHz), 8.19 (dd, 1 H, J I =J2=8.8 Hz), 8.1 S (dd. 1 H, J 1=J2=$.3 Hz). 8.04 (dd, 1 H, J
I=J2=8.8Hz}, 7.91 (dd, 1 H, J I=8.4 Hz, J2=8.8 Hz), 7. 60 (dd, 1 H, J 1=J2=8. I Hz). 5.99 (S, 3H);
Anal. calc'd for C22HtgN40~2.25 C2F302H~2 H20: C, 49.20; H, 3.78; N, 8.66; F, I9.82.
Found: C, 49.02; H, 3.36; N, 8.66.
Example 218 6-(aminoiminomethvl)-N-(3-propox~henvl)-~-naphthalenecarboxamide monoftrifluoroacetate)(salt) 'S Example 218A
3-Aminophenol ( 1 g, 7.2 mmol), triphenylphosphine (2.25 g, 8.6 mmol), and 1-propanol (0.517 g, 8.6 mmol) were dissolved in 25 mL anhydrous THF.
Diethylazodicarboxylate ( 1.S g, 8.6 mmol) was added dropwise over I minute.
The solution was allowed to stir I S minutes and poured slowly into hexanes while stirring.
Filtration through 3o silica gel/celite afforded the product as a viscous yellow oil.
MS (APCI) m/z (M+H)+ 152.
Example 218B

SUBSTtTUTE SHEET (RULE 26) The above product was prepared in the manner of Example i 2 using the product from Example 218A.
MS (APCI} m/z (M+H)+ 331.
Exam lep 2180 6-(aminoiminomethvl)-N-(3~~y Rhenyl)-2-naDhthalPnecarboxamide monoltrifluoroacetate)(sal ) The above was prepared from Example 218 as described in Example 1B.
MS (CI) m/z (M+H)+ 348;
lu ~ H-NMR (300 MHz, d6-DMSO) 8 10.51 (s, 1H), 9.50 (s, 2H), 9.18 (s, 2H), 8.68 (s, 1 H), 8.55 (s, 1 H}, 8.32 (d, 1 H), 8.25-8. I 3 (m, 2H), 7.90 (dd, 1 H), 7.52-7.33 (m, 2H), 7.27 (t, 1 H), 6.73 (dd, 1 H), 3.94 (t, 2H), 1.75 m, 2H), 1.00 {t, 3H) Anal. calc'd for C23H2ZN304F3: 1/20 TFA: C, 59.49; H, 4.77; N, 9.02. Found: C, 59.43; H, 4.94; N, 9.10.
IS
Example 219 6-(aminoiminomethvl)-N-f 3-( 1-ethylpropoxy)phen Iv 1-2-naphthalenecarboxamide mono(trifluoroacetate)(salt~
20 Example 2I9A
The above product was prepared in the manner of Example 218A using 3-pentanol.
MS (APCI) m/z (M+H)+ 18().
Example 219B
25 The above product was prepared in the manner of Example 12 using the product from Example 219A.
MS (APCI) m/z (M+H)+ 359.
Exam 1 19 30 fi~aminoiminomethvl)-N-13-(1-eth~propoxylphenvll-2-naphthalenecarboxamide mono(trifluoroacetate)( alt) The above was prepared from Example 219B as described in Example 1 B.
MS (CI) m/z (M+H)+ 376;

SUBSTITUTE SHEET (RULE 26) WO 99/0509b PCT/US98/15386 IH-NMR (300 MHz, d6-DMSO) b 10.47 (s, IH}, 9.49 (s, 2H), 9.14 (s, 2H), 8.67 (s, 1H), 8.55 (s, I H), 8.31 (d, 1 H), 8.25-8.16 (m, 2H), 7.90 (dd, I H), 7.5 I (s, 1 H), 7.38 (m, 1 H), 7.26 (t, 1H), 6.72 (dd, IH), 4.18 (m, 1H), 1.65 (m, 4H), 0.93 (t, 6H) Anal. calc'd for C25H26N304F3: C, 61.34; H, 5.35; N, 8.58. Found: C, 61.05; H, 5.42; N, 8.22.
Example 220 6-(aminoiminomethvl)-N-13-(cyclopentvlox~phenyll-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) Example 220A
The above product was prepared in the manner of Example 218A using cyclopentanol.
MS (APC1) m/z (M+H)+ 86.
t5 Example 220B
The above product was prepared in the manner of Example I 2 using the product from Example 220A.
MS (APCI) m/z (M+H)+ 357.
2u Example 220C
6-(aminoiminomethvl)-N-f 3-(cyclopentyloxv)phenyll-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) The above was prepared from Example 220B as described in Example 1 B.
MS (CI) m/z (M+H)+ 374;
25 ~ H-NMR (300 MHz, d~-DMSO) 8 10.50 (s, 1 H), 9.51 (s, 2H), 9.30 (s, 2H), 8.68 (s, 1 H), 8.56 (s, I H), 8.32 (d, 1 H), 8.25-8.13 (m, 2H), 7.90 (dd, 1 H), 7.49 (m, I
H), 7.38 (m, 1 H), 7.26 (t, 1 H), 6.72 (dd, 1 H), 4.79 (m, 1 H}, I .96- I .08 (m, 8H}.
Anal. calc'd for C25H24N304F3 2/5 TFA: C, 60.68; H, 5.06; N, 8.49. Found: C, 60.68; H, 5.33; N, 8.65.
Example 221 6-(aminoiminomethyl)-N-(3-phenoxYphenyI)-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTlUS98115386 Examlale 221 A
The above product was prepared in the manner of Example 218A using 3-phenoxyanline.
MS (APCI) m/z (M+H)+ 365.
Example 221 B
6-(aminoiminomethvl)-N-(3- henoxyphenvl)-2-naphthalPnecarboxamide monoltrifluoroacetatel( alts The above was prepared from Example 221A as described in Example 1B.
t0 t H-NMR (300 MHz, d6-DMS O) 8 10.61 (s, I H), 9.50 (s> 2H), 9.20 (s, 2H), 8.66 (s, 1 H), 8.54 (s, 1 H), 8.30 (d, 1 H), 8.22 (d, 1 H), 8.12 (dd, 1 H), 7.90 (dd, 1 H), 7.64-7.57 (m, 2H), 7.46-7.37 (m, 3H), 7.I7 (m, 1H), 7.06 (m, 2H), 6.79 (dd, IH), MS (CI) m/z (M+H)+ 382;
Anal. calc'd for CZ~,H2pN304F3: C, 63.03; H, 4.07; N, 8.48. Found: C, 62.87;
H, 4.24; N, 8.08.
Exam~222 6-(aminoiminomethvl)-N-f3-(phenylmethox~phenyll-2-nanhthalenecarboxamide monoltrifluoroacetate)(salt) 2~t Example 222A
The above product was prepared in the manner of Example 218A using 3-benzyloxyaniline.
MS (APCI) m/z (M+H)+ 379.
Example 222B
6-(aminoiminomethvl)-N-f3-(nhenylmethoxyZphenvll-2-n~phthalenecarboxamide monoltrifluoroacetate)haltl The above was prepared from Example 222A as described in 1B.
MS (CI) m/z (M+H)+ 396;
3c) 1 H-NMR (300 MHz, d6-DMSO) 8 10.53 (s, 1 H), 9.50 (s, 2H), 9.22 (s, 2H), 8.68 {s, I H), 8.55 (s, 1H), 8.31 (d, 1H), 8.23 (d, IH), 8.14 (dd, IH), 7.90 (dd, 1H), 7.61-7.27 (m, 8H), 6.80 (dd, IH), 5.13 (s, 2H) Anal. calc'd for C27H22N304F3: C, 63.65; H, 435; N, 8.25. Found: C, 63.48; H, 4.27; N, 8.07.

SUBSTITUTE SHEET (RULE 26) Exam 1 6-(aminoiminomethvl)-N-l3-ethoxpenyl -) 2-n~, halPnecarboxami~e monoltrifluoroacetate)lsatrl Example 223A
The above product was prepared in the manner of Example 218A using 3-ethoxyaniline.
MS (APC1) m/z (M+H)+ 317.
t~ Example 223B
6-laminoiminomethvl)-N-f3-ethoxymhenyll-2-naphthalenecarboxamide monoltrifluoroacetate)l alt( The above was prepared from Example 223A as described in Example 1B.
MS (CI) m/z (M+H)+ 334;
~ H-NMR (300 MHz, d~,-DMSO) 8 10.52 (s, I H), 9.50 (s, 2H), 9.24 (s, 2H}, 8.68 (s, I H}, 8.55 (s, 1 H), 8.32 (d, 1 H), 8.25-8.13 (m, 2H), 7.90 (dd, I H), 7.51 (m, 1 H), 7.38 (m, 1 H), 7.26 (t, 1 H), 6.72 (dd, 1 H), 4.04 (q, 2H), 1.34 (t, 3H) Anal. calc'd for C22H2pN304F3: C, 59.06; H, 4.SI; N, 9.39. Found: C, 58.69; H, 4.54; N, 9.82.
?t>
Exam Ih a 224 6-laminoiminomethyl)-N-l4-nitro~n ly )-2-naphthalenecarboxamide monoltrifluoroacetate)lsalt) 'S Example 224A
The above product was prepared in the manner of Example 218A using 4-nitroaniline.
MS (APC1) m/z (M+H)+ 3I8.
Example 224B
3(> 6-laminoiminomethvl)-N-l4-nitronhenyl)-2-n~aphthalenecarboxamide monoltrifluoroacetatPll~alt) The above was prepared from Example 224A as described in Example 1 B.
MS (CI) m/z (M+H)+ 335;

SUBSTITUTE SHEET (RULE 26) 1H-NMR (300 MHz, d6-DMSO) 8 / 1.15 (s, IH), 9.55 (s, 2H), 9.22 (s, 2H), 8.77 (s, 1H), 8.58 (s, 1 H), 8.36-8.12 (m, 7H) Anal. calc'd for C2pH15N40gF3 1/10 TFA: C, 52.54; H, 3.29; N, 12.10. Found: C, 53.58;
H, 3.37; N, 12.50.
Example 225 6-(aminoiminomethvl)-N-f 3-(cvclobutvlmethoxy~Dhenvll-2-naphthalenecarboxamide mono(trifluoroacetate)lsalt) Example 225A
The above product was prepared in the manner of Example 218A using cyclobutylmethanol.
MS (APCI} m/z (M+H)+ 177.
5 Example 225B
The above product was prepared in the manner of Example 225A using the product from Example 11 MS (APCI) m/z (M+H)+ 357.
Example 225C
6-(aminoiminomethyl)-N-f 3-(cvclobutylmethoxy?phenyll-2-naphthalenecarboxamide monof trifluoroacetate)(salt) The above was prepared from Example 225B as described in Example 1 B.
MS (CI) m/z (M+H)+ 374;
~ H-NMR (300 MHz, d~,-DMSO) 8 10.50 (s, 1 H), 9.50 (s, 2H), 9.20 (s, 2H), 8.611 (s, 1 H), 8.55 (s, 1H), 8.32 (d, 1H), 8.25-8.13 (m, 2H), 7.90 (dd, 1H), 7.51 (m, 1H), 7.38 (m, 1H), 7.26 (t, 1 H), 6.72 (dd, 1 H), 3.95 (d, 2H), 2. I 1-1.81 (m, 7H);
Anal. calc'd for C25H24N304F3 7/5 TFA: C, 59.09; H, 5.22; N, 8.27. Found: C, 59.02; H, 5.20; N, 8.55.
Example 226 6-(amino(ethoxvcarbonvl)iminol-N-f3-(1-methvlethoxv)phenvll-2 naphthalenecarboxamide The above was prepared from Example 21 lA using method described in Example 216.

SUBSTITUTE SHEET (RULE 26) MS (Cl) mlz (M+H)+ 420;
~H-NMR (300 MHz, d6-DMSO) 8 10.41 (s, IH), 9.24 (br, 2H), 8.67 (s, IH), 8.59 (s, IH), 8.12-7.96 (m, 4H), 7.47 (s, 1H), 7.36 (m, 1H), 7.25 (t, IH), 6.67 (dd, 1H), 4.58 (m, IH), 4.11 (q, ZH), 1.30 (m, 9H) Anal. calc'd for C24H25N304 1/4 H20: C, 67.99; H, 6.06 N, 9.91. Found: C, 67.99; H, 6.07; N, 9.64.
Exam Ip a 227 6-(aminoiminomethvl)-4-f5-(ethvlsulfonyl)-3-furanvll-N-,~he~l-2-n~phthalenecarboxamide monohvdrochloridP
Example 227A
A solution of the product from Example 200C (670 mg, 1.68 mmol) and mCPBA (725 mg, 3.36 mmol) in CH2C12 (25 mL) was stirred for I hour. The reaction was condensed and chromatographed on Si02 using 50% ethyl acetate/hexanes as eluent, to yield 585 mg (81 %) of the desired compound.
MS (DCI/NH3) m/z 448 (M+NH4)+.
Example 227B
6-(aminoiminomethvl)-4-f5-(ethvlsulfonyl)-3-furanyll-N=phenyl-2-naphthalenecarboxamide mono~drochloride The desired compound was prepared from Example 227A and the procedure of Example 13.
MS (DCI/NH3) m/z 448 (M+H)+;
~H NMR (300 MHz, DMSO-d~,) 8 1.29 (t, 3H), 3.50 (y, 2H), 7.16 (t, 1H), 7.42 (t, 2H), 7.83 (d, 2H), 7.95 (dd, I H), 8.05 (s, t H), 8.28 (s, 1 H), 8.43 (d, I H), 8.57 (s, 1 H), k.74 (s, 1 H), 8.79 (s, I H), 9.19 (br s, 2H), 9.59 (br s, 2H), 10.61 (s, 1 H);
Anal. calc'd for C24H22N3S04~ 1.0 HC1~ 1.0 H20: C, 57.43; H, 4.82; N, 8.37.
Found: C, 57.21; H, 5.04; N, 8.34.
Exam le 228 6-laminoiminomethvl)-4-f5-(nro~2vlsulfonyl)-3-furanyll-N-phenyl 2 nanhthalenecarboxamide monohydrochloride SUBSTITUTE SHEET (RULE 26) Examvle 228A
The desired compound was prepared from the product from Example 201C by the procedure of Example 227A.
MS (DCI/NH3) m/z 462 (M+NH~)+.
Exam-ple 228B
6-(aminoiminomethvl)-4-f 5-(nrogvlsulfonyll-3-furan lvhN-phen I-v 2-nanhthalenecarboxamide monohvdrochloride The desired compound was prepared from Example 228A and the procedure of Example to 13.
MS (DCI/NH3) m/z 462 (M+H)+;
1H NMR (300 MHz, DMSO-d6) 8 1.03 (t, 3H), 1. 75 (qt, 2H), 3.48 (q, 2H), 7.16 (t, 1H), 7.41 (t, 2H), 7.84 (d, 2H), 7.95 (dd, IH), 8.05 (s, 1H), 8.28 (d, 1H), 8.42 (d, 1H), 8.58 (s, 1 H), 8.77 (s, 1 H), 8.82 (s, 1 H), 9.28 (br s, 2H), 9.63 (br s, 2H), 10.66 (s, 1 H);
Anal. calc'd for C25H24N3S04~ 1.0 HCI~ I .5 H20: C, 57.20; H, 5.18; N, 8.00.
Found: C, 56.86; H, 5.08; N, 8.28.
Example 229 6-(aminoiminomethvli-4-f5-fmethylthio)methyll-3-furany,-N- henyl-2 naDhthalenecarboxamide monohvdrochloride Example 229A
To a solution of 2-trimethylsilyl-3-bromofuran ( 10.41 g, 47.5 mmol) in THF
(100 mL) at -7R°C was added a I .5 M solution of LDA (34.8 mL, 52.25 mmol), and the reaction was stirred at -78°C for 1 hour. DMF (4.41 mL, 57.0 mmol) was then added, and the reaction was allowed to warm to room temperature and stirred for 1 hour. The reaction was poured into saturated aqueous NH4CI solution, and extracted with 3x diethyl ether. The combined extracts were washed with brine, dried over Na2S04, and condensed. The crude material was taken up in methanol (200 mL) and NaBH4 ( 1.15 g, 24.0 mmol) was added in portions to the stirred solution. After 30 min, the solution was consensed> taken up in pH7 buffer, and extracted with 3x ethyl acetate. The combined extracts were washed with brine, dried over Na2S04, and condensed. The crude product was chromatographed on Si02 using 30% ethyl acetate/hexanes as eluent, to yield 5.52 g (47%) of the desired compound.
MS (DCI/NH3) m/z 250 (M+H)+.

SU6STITUTE SHEET (RULE 26) Example 229B
To a solution of the product from Example 229A (5.52 g, 22.15 mmol) and LiCI ( 1.03 g, 24.36 mmol) in DMF (60 mL) at 0 °C was added PC13 (2.12 mL, 24.36 mmol), and the reaction was stirred at room temperature for 1 hour. The reaction was poured into saturated aqueous NH4Cl solution, and extracted with 3x diethyl ether/hexanes. The combined extracts were washed with 2x water, 2x brine, dried over Na2S04, and condensed to yield 4.70 g (79%) of the desired compound.
t0 Example 229C
A solution of the product from Example 229B (4.70 g, 17.56 mmol) and MeSNa (1.35 g, 19.3 mmol) in DMF (40 mL) was stirred at room temperature for 3 hours. The reaction was poured into saturated aqueous NaHC03 solution, and extracted with 3x Diethyl ether. The combined extracts were washed with brine, dried over Na2S04, and condensed.
The crude ~5 product was chromatographed on Si02 using 30alc ethyl acetate/hexanes as eluent, to yield 4.00 g (82%) of the desired compound.
Example 229D
The desired compound was prepared from the product from Example 229C by the 2U procedure of Example 154B.
MS (DCI/NH3) m/z 30R (Bu3Sn+NH4}+.
Example 229E
The desired compound was prepared from the product from Example D and the product 25 from Example 152C by the procedure of Example 154C.
MS (DCI/NH3) m/z 416 (M+NH4)+.
Exam 1e~229_F
6-laminoiminomethyl)-4-f 5-ff mgthvlthiolmethyll-3-furan~rll-N-phg~l-2-30 nanhthalenecarboxamide monohvdrochloride The desired compound was prepared from Example 229E and the procedure of Example 144C.
MS (DCI/NH3) m/z 416 (M+H)+;

SUBSTITUTE SHEET (RULE 26) 1H NMR (300 MHz, DMSO-d6) b 2.15 (s, 3H), 3.87 (s, 2H), 7.14 (t, IH), 7.40 (t, 2H), 7.84 (d, 2H), 7.92 (dd, 1H), 8.I9 (d, IH), 8.32 (s, 1H), 8.39 (d, IH), 8.64 (s, IH), 8.69 (s, IH), 9.31 (br s, 2H), 9.61 (br s, 2H), 10.62 (s, IH);
Anal. calc'd for C24H21N3S02'I.4 HCI: C, 61.79; H, 4.$4; N, 9.01. Found: C, 61.83; H, 4.82; N, 9.13.
Example 230 6-(aminoiminomethvl)-4-(5-(methoxvmethvl)-3-furan 1~-N~henyl-2-naphthalenecarboxamide mono~drochloride Example 230A
The desired compound was prepared from 2-trimethylsilyl-3-bromofuran and chloromethyl methyl ether by the procedure of Example 154A.
Example 230B
The desired compound was prepared from the product from Example 230A by the procedure of Example I54B.
MS (DCI/NH3) m/z 308 (Bu3Sn+NH4)+.
2o Example 230C
The desired compound was prepared from the product from Example 230B and the product from Example 152C by the procedure of Example 154C.
MS (DCI/NH3) m/z 400 (M+NH4)+.
2S Example 230D
6-(aminoiminomethvl)-4-15-(methoxymethyl)-3-furanvll-Nphenyl-2-naphthalenecarboxamide monohydrochloride The desired compound was prepared from Example 230C and the procedure of Example 144C.
30 MS (DCI/NH3) m/z 400 (M+H)+;
~ H NMR (300 MHz, DMSO-d~,) 8 3.38 (s, 3H), 4.49 (s, 2H), 7.14 (t, 1 H), 7.18 (t, 1 H), 7.40 (t, 2H), 7.84 (d, 2H), 7.92 (dd, 1 H), 8.19 (d, 1 H), 8.38 (d, 1 H), 8.42 (s, I H), 8.64 (s, 1 H), 8.70 (s, lH), 9.32 (br s, 2H), 9.62 (br s, 2H), 10.68 (s, 1H);

SUBSTITUTE SHEET (RULE 26) WO 99/05096 PCTlUS98115386 Anal. calc'd for C24H21N303'2.8 HC1: C, 57.48; H, 4.78; N, 8.38. Found: C, 57.40; H, 4.44; N, 8.38.
Example 23I
6-(aminoiminomethvl)-4-f5-lmethylsulfonyl)-3-furanyll-N- henyl-2-naphthalenecarboxamide mono(trifluoroacetate)(salt) Example 231 A
The desired compound was prepared from the product from Example 152C by the a> procedure of Example 227A.
MS (DCI/NH3) m/z 434 (M+NH4)+.
Example 231 B
6-(aminoiminomethvl)-4-f 5-(methylsulfonvl)-3-furanyll-N-phenyl-2-n~hthalenecarboxamide mono(trifluoroacetate)(salt~
The desired compound was prepared from Example 231 A and the procedure of Example I3.
MS (DCI/NH3) m/z 434 (M+H)+;
~H NMR (300 MHz, DMSO-d6) 8 3.44 (s, 3H), 7.16 (t, 1H), 7.40 (t, 2H), 7.82 (d, 2H), 2c) 7.91 (s, 1 H), 7.95 (dd, I H), 8.00 (s, 1 H), 8.36 (s, 1 H), 8.43 (d, 1 H), 8.57 (s, 1 H), 8.75 (s, 2H), 9.18 (br s, 2H), 9.53 (br s, 2H);
Anal. calc'd for C23H19N3S04~1.0 C2HF302: C, 54.84; H, 3.68; N, 7.67. Found:
C, 55.05;
H, 3.74; N, 7.75.
25 Example 232 6-(aminoiminomethvl)-4-f 5-(ethythio)tetrahydro-~i-furanvll-N-phenyl 2 naDhthalenecarboxamide monohydrochloride Example 232A
3o The desired compound was prepared from the product from Example 152A by the procedure of Example 62A.
MS (DCI/NH3) m/z 315 (M+NH4)+.
Example 232B

SUBSTITUTE SHEET (RULE 26) A solution of the product from Example 232A ( I .62 g, 5.45 mmol), ethanethiol (2.2 mL), and conc. HCl (0.80 mL) in CHCI3 (22 mL) was stirred at room temperature for 3 hours and condensed. The crude product was chromatographed on Si02 using 15% ethyl acetate/hexanes as eluent, to yield I.20 g (6S%) of the desired compound.
MS (DCI/NH3) m/z 359 (M+NH4)+.
Example 232C
The desired compound was prepared from the product from Example 232B by the procedure of Example 152B.
tt> MS (DCI/NH3) m/z 345 (M+NH4)+.
Example 232D
The desired compound was prepared from the product from Example 232C by the procedure of Example 207C.
MS (DCI/NH3) m/z 420 (M+NH4)+.
Example 232E
fi-(aminoiminomethyl)-4-l5-(eth th~trahydro-3-furan, I~-N-phenyl-2 nanhthalenecarboxamide. monohydrochloride 2o The desired compound was prepared from Example 232D and the procedure of Example 144C.
MS (DCI/NH3) m/z 420 (M+H)+;
tH NMR (300 MHz, DMSO-d6) 8 1.18 (dt, 3H), 2.42 (m, 1H), 3.50 (dq, 2H), 3.74 (m, 1H), 3.93 (m, 1 h), 4.39 (m, 1 H), 4.54 (m, i H), 5.38 (dd, O.SH), 5.42 (dd, O.SH), 7.14 (t, 1 H), 7.40 (t, 2H), 7.82 (d, 2H), 7.95 (d, 1 H), 8.06 (s, O.SH), 8.20 (s, 0.5H), 8.32 (d, 1 H), 8.60 (s, 1 H), 8.71 (s, O.SH), 8.80 (s, O.SH), 9.32 (br s, 2H), 9.62 (br s, 2H), 10.59 (br s, 1 H);
Anal. calc'd for C24H25N3~2S~ I.0 HCI: C, 63.22; H, 5.75; N, 9.21. Found: C, 62.93; H, 5.58; N, 9.01.

SUBSTITUTE SHEET (RULE 26)

Claims (16)

WHAT IS CLAIMED IS:
1 . A compound having the formula Z is selected from the group consisting of (1) nitrogen:
(2) methine: and (3) methine substituted with -NR1R2;
A is selected from the group consisting of (1) hydrogen and (2) -L A R A;
B is selected from the croup consisting of (1) hydrogen and (2) -L B R B and C is selected from the group consisting of (1) hydrogen and (2) -L C R C, with the proviso that at least one of A. B or C is other than hydrogen; and with the proviso that when A is other than hydrogen, at least one of B or C is other than hydrogen, wherein for A, B, and C, L A, L B and L C are independently selected from the group consisting of (1) a covalent bond.
(2) -(CH2)m-(3) -NR1-, (4) -NR2C(X)NR3-, (5) -C(X)-, (6)-NR2C(X)-, (7)-C(X)NR2-, (8)-CH=CH-, (9)-C~C-, (10)-O-, (11) S(O)1-(12)-C=C(CH2)nNR2C(X)-, (13)-C(X)NR2(CH2)nC~C-, (14)-(CH2)nNSO2-, (15)-NR2SO2(CH2)nC~C-, (16)-C~C(CH2)nNR2SO2NR3-, (17)-NR2SO2NR3(CH2)nC~C-, (18)-SO2NR2-, (19)-NR2SO2 (20)-NR2SO2NR3-, (21)-N=N-, (22)-C(X)N(OR2)-, (23)-N(OR2)C(X)-, (24)-HC=CH(CH2) n NR2C(X)-, (25)-(CH2)nNR2C(X)CH=CH-, (26)-CH=CH(CH2) n NSO2-, (27)-NR2SO2(CH2) n CH=CH-, (28)-(CH2) n NR2SO2NR3-, (29)-NR2SO2NR3(CH2)nCH=CH-, (30)-NR2C(O)O-, (31)-OC(O)NR2-, (32)-CH=NO-, (33)-ON=CH- and (34) , wherein W is selected from the group consisting of (a) -O-, (b) -S-, (c) -NR1- and (d) -(CH2)m-, wherein each functional group is depicted with its right-hand end being the end which is attached to the naphthyl or quinolyl ring and its left-hand end being the end which is attached to R A, R B or R C;
R A, R B and R C are independently selected from the group consisting of (1) aryl:
(2) arylalkoxy, wherein the alkylene group is of one to six carbon atoms:
(3) alkyl of one to ten carbon atoms:
(4) alkenyl of two to ten carbon atoms;
(5) alkoxycarbonyl of one to six carbon atoms;
(6) alkynyl of two to ten carbon atoms:
(7) halogen:
(8) -NR1R2:
(9) heterocycle:
(10) cycloalkenyl of four to twelve carbon atoms;
(11) cycloalkyl of three to twelve carbon atoms:
(12) -NR1C(O)NR2R3; and (13) -NR1C(O)R50, wherein R50 is alkyl of one to six carbon atoms;
wherein, at each occurence, R1 is selected from the group consisting of (1) hydrogen;
(2) an N-protecting group;
(3) alkyl of one to six carbon atoms:
(4) alkenyl of two to six carbon atoms;
(5) alkynyl of two to six carbon atoms:
(6) aryl;
(7) arylalkyl, wherein the alkylene group is of one to six carbon atoms;
(8) cycloalkyl of three to eight carbon atoms and (9) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms. and the alkylene group is of one to ten carbon atoms; and wherein, at each occurence. R2 and R3 are independently selected from the group consisting of (1) hydrogen;
(2) alkyl of one to six carbon atoms;

(3) alkenyl of two to six carbon atoms:
(4) alkynyl of two to six carbon atoms:
(5) aryl:
(6) arylalkyl, wherein the alkylene group is of one to six carbon atoms (7) cycloalkyl of three to eight carbon atoms and (8) cycloallcylalkyl wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms: and wherein. at each occurence. X is selected from the group consisting of (1) O and (2) S; and wherein, at each occurence.
m is one to five, n is zero to four and t is zero to two: and wherein, at each occurence, the alkyl, alkenyl, alkynyl. aryl, heterocycle, cycloalkyl, and cycloalkenyl groups are optionally substituted.
2. A compound according to Claim 1 wherein A and C are hydrogen and B is -L B R B.
3. A compound according to Claim 2 selected from the group consisting of 7-(2-hydroxyethoxy)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt:
methyl 5-[7-[(aminoiminomethyl 1-2-naphthalenyl]oxy]pentanoate:
mono(trifluoroacetate) salt:
5-[[6-(aminoiminomethyl)-2-naphthalenyl]oxy)pentanoic acid, mono(trifluoroacetate) Salt;
methyl 4-[[[7-amino(hydroxyimino)methyl]-2-naphthalenyl]oxy]ethyl]benzoate;
methyl 2-[[6-(aminoiminomethyl)-2-naphthalenyl]oxy]acetate, mono(trifluoroacetate) salt:
7-[2-(4-morpholinyl)ethoxy]-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt:
2-[[6-(aminoiminomethyl)-2-naphthalenyl]oxy]acetic acid, mono(trifluoroacetate) salt;
and methyl 4-[6-(aminoiminomethyl)-2-naphthalenyl)oxy]methyl]benzoate, mono(trifluoroacetate) salt.
4. A compound according to Claim 1 wherein A and B are hydrogen; and C is -L C R C
5. A compound according to Claim 4 selected from the group consisting of 8-(carbonylbenzyloxy)amino-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl)acetamide mono(trifluoroacetate) salt;
methyl [7-(aminoiminomethyl)-I-naphthalenyl)carbamate mono(trifluoroacetate) salt;
methyl 3-([7-(aminoiminomethyl)-I-naphthalenyl]amino]-3-oxopropionate mono(trifluoroacetate) salt:
N-[7-(aminoiminomethyl)-1-naphthalenyl)-2-(phenylmethoxy)acetamide mono(trifluoroacetate) salt:
N-[7-(aminoiminomethyl)-1-naphthalenyl]-1,3-benzodioxole-5-carboxamide mono(trifluoroacetate) salt, N-[7-(aminoiminomethyl)-1-naphthalenyl]benzenemethanesulfonamide mono(trifluoroacetate) salt, methyl[7-(aminoiminomethyl)-1-naphthalenyl]methylcarbamate, mono(trifluoroacetate) salt;
propyl[7-(aminoiminomethyl)-1-naphthalenyl]carbamate, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl]-N'-methylurea, mono(trifluoroacetate) salt;
ethyl [7-(aminoiminomethyl)-1-naphthalenyl)carbamate, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl)propanamide, mono(trifluoroacetate) salt;
N-(7-(aminoiminomethyl)-1-naphthalenyl)-2-methoxyacetamide, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl]urea, mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl]-2-hydroxyacetamide, mono(trifluoroacetate) salt;
8-(2-pyrimidinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
8-amino-2-napthalenecarboximidamide. bis(trifluoroacetate) salt;
8-(2-pyridinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
and N-hydroxy-8-(2-pyrimidinylamino)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt.
6. A compound according to Claim 1 wherein A is -L A R A, B is -L B R B, and C is hydrogen.
7. A compound according to Claim 6 which is 6, 7-Dimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt.
8. A compound according to Claim 1 wherein A is -L A R A;
B is hydrogen: and C is -L C R C.
9. A compound according to Claim 8 selected from the group consisting of methyl 6-(aminoiminomethyl)-4-[(methoxycarbonyl)amino]-2-naphthalenecarboxylate mono(trifluoroacetate) salt;
6-methoxy-8-benzyloxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
2-((7-aminoiminomethyl-3-methoxy-1-naphthalenyl)oxy] acetamide mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-4-l3-furanyl)-N-(4-(trifluoromethyl)phenyl]-2-naphthalenecarboxamide, mono(trifluoroacetate) salt:
6-(aminoiminomethyl)-4-(3-furanyl)-N-(4-pyridinyl)-2-naphthalenecarboxamide, dihydrochloride;
6-(aminoiminomethyl)-4-(3-furanyl)-N-(1H-pyrazol-3-yl)-2-naphthalenecarboxamide, dihydrochloride:
6-(aminoiminomethyl)-4-(3-furanyl)-N-(3-pyridinyl)-2-naphthalenecarboxamide, dihydrochloride;
methyl [7-(aminoiminomethyl)-3-[[[4-(aminomethyl)phenyl]amino]carbonyl]-1-naphathalenyl]carbamate, bis(trifluoroacetate) salt;

6-(aminoiminomethyl)-4-(3-furanyl)-N-(2-pyridinyl)-2-naphthalenecarboxamide, dihydrochloride;
6-(aminoiminomethyl)-4-(3-furanyl)-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
6-(aminoiminomethyl)-4-[1-(methylsulfonyl)-1H-pyrazol-4-yl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
6-(aminoiminomethyl)-4-[5-(methylthio)-3-furanyl)]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
6-(aminoiminomethyl)-N-[4-(aminomethyl)phenyl]-4-(2-pyrimidinylamino)-2-naphthalenecarboxamide, tris(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-phenyl-4-(2-pyrimidinylamino)-2naphthalenecarboxamide, mono(trifluoroacetate)salt:
N-[(4-(aminomethyl)phenyl]-6-[amino(hydroxyimino)methyl]-4-(2-pyrimidinylamino)-2-naphthalenecarboxamide, bis(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-[4-(hydroxymethyl)phenyl]-4-(2-pyrimidinylamino)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
methyl [3-[[[4-(aminomethyl)phenyl)amino]carbonyl]-7-[4-amino(hydroxyimino)methyl]-1-naphthalenyl)carbamate, bis(trifluoroacetate) salt;
6-(aminoiminomethyl)-N-phenyl-4-(tetrahydro-3-furanyl)-2-naphthalenecarboxamide,monohydrochloride;
6-[amino(hydroxyimino)methyl]-N-phenyl-4-(2-pyrimidinylamino)-2-naphthalenecarboxamide;
6-(aminoiminomethyl)-4-[5-(ethylthio)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide,monohydrochloride;
6-(aminoiminomethyl)-4-[5-(propylthio)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide.monohydrochloride;
6-(aminoiminomethyl)-N-phenyl-4-(2-pyrrolidinyl)-2-naphthalenecarboxamide, mono(trifluoroacetate) salt;
6-(aminoiminomethyl)-4-[5-(propylsulfonyl)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
6-(aminoiminomethyl)-4-[5-[methylthio)methyl]-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;
6-(aminoiminomethyl)-4-[5-(methoxymethyl)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(aminoiminomethyl)-4-(5-(methylsulfonyl)-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, mono(trifluoroacetate) salt; and 6-(aminoiminomethyl)-4-[S-(ethythio)tetrahydro-3-furanyl]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride.
10. A compound according to Claim 1 wherein A is -L AR A, B is -L B R B, and C is -L C R C.
11. A compound according to Claim 10 which is 6, 7, 8-trimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt.
12. A compound according to Claim 1 wherein A is hydrogen;
B is -L B R B; and C is -L C R C.
13. A compound according to Claim 12 selected from the group consisting of 7, 8-Dimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt:
2-[(7-aminoiminomethyl)-2-methoxy-1-naphthalenyl foxy]acetamide mono(trifluoroacetate) salt;
7-benzyloxy-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
methyl [(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]acetate mono(trifluoroacetate) salt:
2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-yl-acetic acid mono(trifluoroacetate) salt;
1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-hydroxypropane mono(trifluoroacetate) salt;
1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-bromopropane mono(hydrochloride) salt;
3-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]propene mono(trifluoroacetate) salt;

1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-phenylpropane mono(hydrochloride) salt;
1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-[1-(3,4-dimethoxy)phenyl]propane mono(hydrochloride) salt;
7-methoxy-8-(2-furanyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
(E)-[7-methoxy-8-[2-(phenyl)ethenyl])-2-naphthaleneimidamide mono(trifluoroacetate) salt 7-(2-hydroxyethoxy)-8-iodo-2-naphthalenecarboximidanude mono(trifluoroacetate) salt;
7-propoxy-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-(1H-pyrazol-4-yl)-2-naphthalenecarboximidamide bis(trifluoroacetate) salt;
7-methoxy-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt 7-methoxy-8-(3-furanyl)-2-naphthalenecarboximidamide mono(methanesutfonate) salt;
7-methoxy-8-(2-benzofuranyl)naphthalene-2-carboximidamide mono(methanesulfonate) salt;
(E)-8-[2-(1,3-benzodioxol-5-yl)ethenyl]-2-naphthalenecarboximidamide mono(methanesulfonate) salt;
(~)-7-methoxy-8-(tetrahydro-3-furanyl)-2-naphthalenecarboximidamide mono(methanesulfonate) salt;
7-methoxy-8-[2-pyrimidinyl(oxy)]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-[2-thiazoyl(oxy)]naphthalene-2-carboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-(4-nitrophenoxy)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-pentafluorophenoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-[N-2-pyrimidinyl(amino)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
4-[7-(aminoiminomethyl)-2-methoxy-1-naphthalenyl]dihydro-2(3H)-furanone mono(trifluoroacetate) salt;
7-methoxy-8-(1-acetyl-1H-pyrazolyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;

7-methoxy-8-[1-(methylsulfonyl)-1H-4-pyrazolyl]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
6-[2-(4-aminophenyl)ethoxy]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
methyl[3-methoxy-6-(aminoiminomethyl)-4-naphthalenyl]carbamate mono(trifluoroacetate) salt;
7-methoxy-8-[2-pyrimidinyl(amino)]-2-naphthalenecarboximidamide bis(trifluoroacetate) salt;
methyl[7-(aminoiminomethyl)-2-methoxy-1-naphthalenyl)carbamate, mono(trifluoroacetate) salt;
7-methoxy-8-(2-pyrimidinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt;
7-methoxy-8-[(phenylmethyl)amino]-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
7-methoxy-8-(phenylamino)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
7-methoxy-8-[(4-methoxyphenyl)amino]-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
(E)-3-[7-(aminoiminomethyl)-2-methoxy-1-naphthalenyl)-2-propenamide, mono(trifluoroacetate) salt;
7-methoxy-8-(3-oxo-1-cyclopenten-1-yl)-2-naphthalenecarboximidamide, mono(trifluoroacetate) salt;
methyl 4-[[[7-(aminoiminomethyl)-1-(2-pyrimidinylamino)-2-naphthalenyl]oxy]methyl]benzoate, mono(trifluoroacetate) salt;
4-[[[7-(aminoiminomethyl)-1-(2-pyrimidinylamino)-2-naphthalenyl]oxy]methyl]
benzoic acid, mono(trifluoroacetate) salt;
7-methoxy-8-(pyrazinyloxy)-2-naphthalenecarboximidamide, dimethanesulfonate salt;
7-methoxy-8-(phenylthio)-2-naphthalenecarboximidamide, methanesulfonate; and 7-methoxy-8-(pyrazinylamino)-2-naphthalenecarboximidamide, bis(trifluoroacetate) salt.
14. A compound selected from the group consisting of 7, 8-dimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
6, 7, 8-trimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;

6, 7-dimethoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy] acetamide mono(trifluoroacetate) salt;
7-benzyloxy-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
methyl [(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]acetate mono(trifluoroacetate) salt;
2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-yl-acetic acid mono(trifluoroacetate) salt;
I-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-hydroxypropane mono(trifluoroacetate) salt;
phenylmethyl[7-(aminoiminomethyl)-1-naphthalenyl)carbamate mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-I-naphthalenyl)acetamide mono(trifluoroacetate) salt;
methyl [7-(aminoiminomethyl)-1-naphthalenyl)carbamate mono(trifluoroacetate) salt:
methyl 3-[[7-(aminoiminomethyl)-1-naphthalenyl]amino]-3-oxopropanoate mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl]-2-(phenylmethoxy)acetamide mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl]-1,3-benzodioxole-5-carboxamide mono(trifluoroacetate) salt;
N-[7-(aminoiminomethyl)-1-naphthalenyl]benzenemethanesulfonamide mono(trifluoroacetate) salt;
1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy)-3-bromopropane mono(hydrochloride) salt;
3-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]propene mono(trifluoroacetate) salt;
1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-phenylpropane mono(hydrochloride) salt;
1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl)oxy]-3-[1-(3,4-dimethoxy)phenyl]-propane mono(hydrochloride) salt;
7-methoxy-8-(2-furanyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
methyl 6-(aminoiminomethyl)-4-[(methoxycarbonyl)amino]-2-naphthalenecarboxylate mono(trifluoroacetate) salt;
(E)-6-[2-(phenyl)ethenyl]-2-naphthaleneimidamide mono(trifluoroacetate) salt;

7-(2-hydroxyethoxy)-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-(2-hydroxyethoxy)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
6-methoxy-8-benzyloxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
2-[(7-aminoiminomethyl-3-methoxy-1-naphthalenyl)oxy]acetamide mono(trifluoroacetate) salt;
7-propoxy-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate} salt;
7-methoxy-8-(1H-pyrazol-4-yl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-iodo-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-(3-furanyl)-2-naphthalenecarboximidamide mono(methanesulfonate) salt;
7-methoxy-8-(2-benzofuranyl)naphthalene-2-carboximidamide mono(methanesulfonate) salt;
(E)-8-[2-(1,3-benzodioxol-5-yl)ethenyl]-2-naphthalenecarboxinudamide mono(methanesulfonate) salt;
(~)-7-methoxy-8-(tetrahydro 3-furanyl)-2-naphthalenecarboximidamide mono(methanesulfonate) salt;
7-methoxy-8-[2-pyrimidinyl(oxy)]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-[2-thiazoyl(oxy)]naphthalene-2-carboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-(4-nitrophenoxy)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-pentafluorophenoxy-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-(N-2-pyrimidinyl(amino)]-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-benzylurea mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-methylurea mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-isopropylurea mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-phenyl-N'-methylurea mono(trifluoroacetate) salt;
6-aminonaphthalene-2-carboximidamide mono(trifluoroacetate) salt;

N-(6-aminoiminomethyl-2-naphthalenyl)-N'-cyclohexylurea mono(trifluoroacetate) salt;
N-(6-aminoiminomethyl-2-naphthalenyl)-N'-benzyloxyurea mono(trifluoroacetate) salt;
1,1-dimethylethyl [4-[[(6-cyano-2-naphthalenyl)amino]carbonyl)phenyl)carbamate mono(trifluoroacetate) salt N-(6-(aminoiminomethyl)-2-naphthalenyl]-4-(aminomethyl)benzamide mono(trifluoroacetate) salt;
4-[7-(aminoiminomethyl)-2-methoxy-1-naphthalenyl]dihydro-2(3H)-furanone mono(trifluoroacetate) salt:
7-methoxy-8-( 1-acetyl-1 H-pyrazolyl)-2-naphthalenecarboximidamide mono(trifluoroacetate) salt;
7-methoxy-8-[1-(methylsulfonyl)-1H-4-pyrazolyl]-2-naphthalenecarboximidamide mono(trifluoroacecate) salt:
methyl [3-methoxy-6-(aminoiminomethyl)-4-naphthalenyl]carbamate mono(trifluoroacetate) salt;
7-methoxy-8-[2-pyrimidinyl(amino)]-2-naphthalenecarboximidamide; and bis(trifluoroacetate) salt.
15. A method for inhibiting urokinase in a mammal in need of such treatment, comprising adminstering to the mammal a therapeutically effective amount of a compound of Claim 1.
16. A composition for inhibiting urokinase comprising both a pharmaceutical carrier and a therapeutically effective amount of a compound of Claim 1.
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