REISSERT COMPOUNDS AS ANTI-HIV AGENTS

Abstract: Disclosed are heterocyclic compounds of formula (I). The compounds of the invention are useful in the treatment of AIDS and AIDS related complex. The compounds of the invention are generally synthesized by following the reactions and conditions used to make Reissert compounds. Compounds included within the scope of formula (I) are 1,2-dihydroquinolines, 1,4-dihydroquinolines, 1,2,3,4-tetrahydroquinolines, 1,2-dihydroquinazolines, and the 1,2-dihydroquinoxalines. Representative compounds include 1-(4-bromobenzoyl)-2-cyano-1,2-dihydroquinoline, 1-(4-chlorobenzoyl)-2-cyano-5-fluoro-1,2-dihydroquinoline, 1-(4-chlorobenzoyl)-2-cyano-6-fluoro-1,4-dihydroquinoline, 1-(4-chlorobenzoyl)-2-cyano-1,2,3,4-tetrahydroquinoline, 1-(4-chlorobenzoyl)-2-carboximidamide-8-fluoro-1,2-dihydroquinoline, 1-(4-chlorobenzoyl)-2-cyano-1,4-dihydroquinoxaline, 1-E-(3-(4-chlorophenyl)-1-oxo-2-propenyl)-2-cyano-1,2-dihydroquinoline, and 1-E-(3-(4-chlorophenyl)-1-oxo-2-propenyl)-2-carboximidamide-1,2-dihydr oquinoline. Also included within the scope of the invention is a method of treating a human having AIDS or ARC with an effective amount of a compound of the invention.

Description: REISSERT COMPOUNDS AS ANTI-HIV AGENTS Field of the Invention This invention provides novel 1,2-dihydroquinolines, 1,4-dihydroquinolines, 1,2,3,4- tetrahydroquinolines, 1,2-dihydroquinazolines, and 1,2-dihydroquinoxalines, as well as known compounds of these classes, which are useful as anti-AIDS drugs. Background of the Invention An estimated one to one and one-half million people in the United States are infected with a human retrovi us, the human immunodeficiency virus type I (HIV-1) which is the etiological agent of acquired immunodeficiency syndrome, AIDS, see Science, 661-662 (1986). Of those infected, an estimated two hundred and fifty thousand people will develop AIDS in the next five years, see Science, 1352-1357 (1985). On March 20, 1987, the FDA approved the use of the compound, AZT (zidovudine), to treat AIDS patients with a recent initial episode of pneumocystis carinii pneumonia, AIDS patients with conditions other than pneumocystis carinii pneumonia or patients infected with the virus with an absolute CD4 lymphocyte count of less than 200/mm 3 in the peripheral blood. AZT is a known inhibitor of viral reverse transcriptase, an enzyme necessary for human immunodeficiency virus replication. U.S. Patent 4,724,232 claims a method of treating humans having acquired immunodeficiency syndrome utilizing 3'-azido-3'-deoxy-thymidine (azidothymidine, AZT). It is known in the art that certain antibiotics and polyanionic dyes inhibit retrovirus reverse transcriptase. It has also been reported that various sulfated compounds inhibit virus replication, including HIV. Information Disclosure F.D. Popp, "Reissert Compounds and Related N-acyldihydroquinolines" in Quinolines, Part II, Ed. G. Jones, (1982) p. 353-372, is a general review covering the synthesis and reactions of Reissert compounds. This review also specifically describes the synthesis of l-(4- chlorobenzoyl)-2-cyano-l ,2-dihydroquinoline, 1 -(4-fluorobenzoyl)-2-cyano-l ,2- dihydroquinoline, l-(4-methoxybenzoyl 2-cyano-l,2-<lihydroquinoline, l-(4-toluoyl)-2-cyano- 1 ,2-dihydroquinoline, l-(4-nitrobenzoyl)-2-cyano-l ,2-dihydroquinoline, l-(2-naphthoyl)-2- cyano-l,2-dihydroquinoline, and l-(l-oxo-3-phenyl-2-propenyl)-2-cyano-l,2-dihydroquinoline. F.D. Popp, W. Blount and P. Melvin, l Q∑&. Chem.. 26, 4930 (1961), describes the methylene chloride/water method for synthesizing Reissert Compounds. S. Ruchirawat, N. Phadungkul, M. Chuankamnerdkarn, and C. Thebtaranonth, Heterocycles. 6, No. 1, 43 (1977), describes the trimethylsilyl cyanide method of synthesizing Reissert compounds. M. Rozwadowska, Roczniki Chemii. 51, 2321 (1977), describes hydrogenation of dihydroquinoline Reissert compounds to tetrahydroquinolines. L. Walters, M. Siegel, and R. Cook, I. Heterocyclic Chem.. 5,577 (1968), describes synthesis of amidoximes via addition of hydroxylamine to a Reissert compound. H. Bartsch, O. Schwarz, and G. Neubauer, Heterocycles. 24, 3483 (1986), describes die synthesis of a benzoxazine Reissert compound. F. Elroy and R. Lenaers, "The Chemistry of Amidoximes and Related Compounds," Chem. Rev. 155 (1962), describes synthesis and reactions of .amidoximes. Uff, B.C., Budhram, R.S., Consterdine, M.F., Hicks, J.K., and Slingsby, B.P., J. Chem. Soc. Perkins Trans I (18): 2018-22 (1977), describes synthesis of 2-cyano-l-(4- methoxybenzoyl)-4-methyl-l ,2-dihydroquinoline. F.D. Popp and A. Soto, ∑. Chem. Soc. 1760 (1963), describes the synthesis of l-(4- fluorobenzoyl)-2-cyano-l,2-dihydroquinoline. Japanese Patent Application JO 2049-782-A, discloses quinolidine compounds which are stated as useful in treating AIDS. These quinolidines are not structurally related to the compounds of the present invention. SUMMARY OF THE INVENTION This invention provides compounds of formula I wherein R 2 is -CN, -N 3 , -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C j -C 4 alkyl, -Ac, -C(O)OCH 3 , -C(O)OC 2 H 5 , -phenyl, -PO 2 -O " cation + , -CO-CH(AA)NH 2 , -CO-C 6 H 6 -NR π R 12 , and -CO-C 6 H 6 -CH 2 -NR n R 12 ; AA is -CH 3 , -CH(CH 3 ) 2 , -CH 2 CH(CH 3 )2,-CH 2 OH, -CH(OH)CH 3 , -CH^C^H, -CH 2 CH 2 CO2H, -(CH2) 4 NH 2 , and -(CH2) 3 -NH 2 ; Rn and R 1 m y be the same or different and are hydrogen and C j -C 4 alkyl; Rn and R 12 taken together are morpholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N-(C!-C 4 alkyl)piperazinyl; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen, C r C 4 alkyl, -(CH^CN, and -(O^R^; R 13 is -N(CH 3 ) 2 , -OH, -OPO 3 H, -OCH 2 CH(-OH)CH 2 OH, -OO^CC^H, -O^fCH^CO j H, -OR 14 , and -NR 14 ; R 14 is a N-terminal amino acid; a is zero to six; b is one to five; A is CH, CH 2 , N, and CHN^H^; X is CH, CH 2 , NH, O, and C-R 4 ; R 4 is -CH 3> -OCH 3 , and -OAc; R5, R 6 , R 7 , and R 8 may be the same or different and are hydrogen and fluorine; W is oxygen and sulfur; Z is a direct bond or a linker selected from the group consisting of -(CO)-, -CH =CH-CH=CH- (all E), -CR 15 =CR 16 - (E or Z), and -CH =C=CH-; R 15 and R 16 may be the same or different and are hydrogen and fluorine; Y { is hydrogen, -Cl, -F, -Br, -CH 3 , -CF 3 , -(CH 2 ) C R 17 , -CHO, -CO j CH j , -OH, -OCH 3) -OAc, -CN, -NO2, -SH, and -SCH 3 ; c is zero to five; R 17 is -CH 2 N(CH 3 )2, -OH, -OPO 3 H, -CH 2 N(C 2 H 5 ) 2 , -O-sugar, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 CCH2CH 2 CO 2 H, -CH 2 N= CHN(CH 3 )2, -OR 18 , OR -NR 18 ; R j g is an N-terminal amino acid; Y 2 is hydrogen, -F, -Cl, -OCH3, and -CF 3 ; Y j and Y 2 taken together can form -OCH 2 O-, -OC(CH 3 )2O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S-, -SCH 2 O-, and -CH = CR 19 -CH = CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, when Z is a direct bond and A and X are each CH, and R 5 , Rg, R 7 , and Rg are each hydrogen, and R 2 is -CN, Y j is not -Cl, -F, or -CH 3 and R 19 is not hydrogen, when Z is a direct bond and R 2 is -C(=NOH)N(R 10 )H and R 10 is hydrogen, R 19 is not hydrogen, when Z is a direct bond, Y j is not hydrogen, when Z is -CR 15 =CR 16 - (E), and Y 2 , R^, and R 16 are each hydrogen, Y j is not hydrogen, when Y j is -OCH 3 and Z is a direct bond, at least one of R5, Rg, R 7 or R 8 is fluorine, when Y ] is -CF 3 and Z is direct bond, the connection between positions 3 and 4 is a double bond, when Z is a direct bond, X is not 0, when Z is a direct bond, R 2 is not -N 3 , when Z is a direct bond, Y 2 is hydrogen, when A is N, X is C-R 4 and R 4 is -OCH 3 , or -OAc and the connection between position 3 and 4 is a double bond, when A is CHN(CH 3 )2, X is CH 2 , when R is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Y λ is -Cl, -F, -Br, -CF 3 , -CN, or -NO 2 , when R 5 is fluorine, Rg, R 7 and R 8 are each hydrogen, when Y j and Y 2 taken together are -CH=CR 19 -CH=CH-, Z is a direct bond, and when Y j and Y 2 taken together can form -OCH 2 0-, -OCiCH O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S-, and -SCH 2 O-, Z is a linker; or the pharmaceutically acceptable salts thereof. The preferred compound is l-E-(3-(4-chlorophenyI)-l-oxo-2-propenyl)-2-cyano-l,2- dihydroquinoline. The invention further provides compounds of formula II wherein R 2 is -CN, -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C r C 4 alkyl, -Ac, -C(O)OCH 3 , -C(O)OC 2 H 5 , -phenyl, -PO 2 -O" cation "1" , -CO-CH(AA)NH 2 , -CO-C 6 H 6 -NR n R 12 , and -CO-C 6 H 6 -CH 2 -NR π R 12 ; AA is -CH 3 , -CH(CH 3 )2, -CH 2 CH(CH 3 )2,-CH 2 OH, -CH(OH)CH 3 , -CH 2 CO 2 H, -CH 2 CH 2 CO2H, -(CH 2 ) 4 NH 2 , and -(O^-NH^ RJJ and R 12 may be the same or different and are hydrogen and C j -C 4 alkyl; Rn and R 12 taken together are morpholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N-(C j -C alkyl)piperazinyl; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen, C x -C 4 alkyl, -(CH^CN, and -(CH2)bR 13 ; R 13 is -N(CH 3 ) 2 , -OH, -OPO 3 H, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O^CH^CC^H, -OR 14 , and -NR 14 ; R 14 is a N-terminal amino acid; a is zero to six; b is one to five; A is CH, CH 2 , and CHN^H^; X is CH, CH 2 , and C-R 4 ; R 4 is -CH 3 , -OCH 3 , and -OAc; R 5 , Rg, R 7 , Rg may be the same or different and are hydrogen and fluorine; W is oxygen and sulfur; Y j is -Cl, -F, -Br, -CH 3 , -CF 3 , -(CH^R^ -CHO, -CO 2 CH 3 , -OH, -OCH 3 -OAc, -CN, -NO j , -SH, and -SCH 3 ; c is zero to four; R I7 is -CH 2 N(CH 3 ) 2 , -OH, -OPO 3 H, -CH 2 N(C 2 H 5 ) 2 , -O-sugar, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 CCH 2 CH 2 CO 2 H, -OR 18 , and -NR 18 ; R j g is a N-terminal amino acid; Y 2 is hydrogen; Y j and Y 2 taken together are -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, when A and X are each CH, and R5, Rg, R 7 , and R g are each hydrogen, and R 2 is -CN, Y j is not -Cl, -F, or -CH 3 and R 19 is not hydrogen, when R 2 is -C(=NOH)N(R 10 )H and R 10 is hydrogen, R 19 is not hydrogen, when Y j is -OCH 3 , at least one of R 5 , Rg, R 7 or R 8 is fluorine, when Y j is -CF 3 , the connection between positions 3 and 4 is a double bond, when R 4 is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Y! is -Cl, -F, -Br, -CF 3 , -CN, or -NO 2 , and when R 5 is fluorine, Rg, R 7 and Rg are each hydrogen, or the pharmaceutically acceptable salts thereof. Further provided is a compound of formula II wherein R 2 is -CN, -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C j -C 4 alkyl, -Ac, -C(O)OCH 3 , -C(O)OC 2 H 5 , -phenyl, -PO 2 -O _ cation + , -CO-CH(AA)NH 2 , -CO-C 6 Hg-NR π R 12 , and -CO-CgH 6 -CH 2 -NR u R 12 ; AA is -CH 3 , -CH(CH 3 )2, -CH 2 CH(CH 3 )2,-CH 2 OH, -CH(OH)CH 3 , -C^CC^H, -CH 2 CH 2 CO 2 H, -(CH 2 ) 4 NH 2 , and -(CH 2 ) 3 -NH 2 ; Rn and R 12 may be the same or different and are hydrogen and C j -C 4 alkyl; RJ J and R j2 taken together are morpholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N-(C j -C 4 alky piperazinyl; A is CH, CH 2 , and N; X is C-I^, and NH; R 4 is -CH 3 -OCH 3 , and -OAc; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen; R 5 , Rg, R 7 , R 8 may be the same or different and are hydrogen and fluorine; W is oxygen; Y j is -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OCH 3j -OAc, -CN, -NO j , -SH, and -SCH 3 ; Y 2 is hydrogen; Y- and Y 2 taken together are -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, when Y! is -OCH 3 , at least one of R 5 , R 6 , R 7 or R 8 is fluorine, when Y ] is -CF 3 , the connection between positions 3 and 4 is a double bond, when A is N, X is C-R 4 and R is -OCH 3 or -OAc and the connection between position 3 and 4 is a double bond, when R 4 is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Yi is -Cl, -F, -Br, -CF 3 , -CN, or -NO 2 , and when R5 is fluorine, Rg, R 7 and Rg are each hydrogen; or the pharmaceutically acceptable salts thereof. The invention further provides compounds of formula I wherein R 2 is -CN, -N 3 , -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR I0 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C^ alkyl, -Ac, -C(O)OCH 3 , -C(O)OC 2 H 5 , -phenyl, -PC^-O " cation + , -CO-CH(AA)NH 2 , and ■ CO-C 6 K 6 -CΑ τ m-u R l2 > AA is -CH 3 , -CH(CH 3 )2, -CH 2 CH(CH 3 )2,-CH 2 OH, -CH(OH)CH 3 , -CH 2 CO 2 H, -CH^H j CC^H, -(CH2) 4 NH 2 , and -(CH 2 ) 3 -NH 2 ; R π and R 12 may be the same or different and are hydrogen and Cι~C 4 alkyl; R tl and R 12 taken together are morpholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N-(C t -C 4 alkyl)piperazinyl; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen, C^ alkyl, -(CH^CN, and -(CH^R^; R 13 is -N(CH3) 2 , -OH, -OPO 3 H, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O^CH^CC^H, -OR 14 , and -NR 14 ; R 1 is a N-terminal amino acid; a is zero to six; b is one to five; A is CH, CH 2 , and CHN(CH 3 ) 2 ; X is CH, CH 2 , and C-R 4 ; R 4 is -CH 3 , -OCH 3 , and -OAc; R 5 , Rg, R 7 , and Rg may be the same or different and are hydrogen and fluorine; W is oxygen and sulfur; Z is a linker selected from the group consisting of -(CO)-, -CH=CH-CH=CH- (all E), -CR 15 =CR 16 - (E or Z), or -CH=C=CH-; R 15 and R j may be the same or different and are hydrogen and fluorine; Y j is hydrogen, -Cl, -F, -Br, -CH 3 , -CF 3 , -(CH 2 ) C R 17 , -CHO, -CO 2 CH 3 , -OH, -OCH 3> -OAc, -CN, -NO j , -SH, and -SCH 3 ; c is zero to five; R 17 is -CH 2 N(CH 3 ) 2 , -OH, -OPO 3 H, -CH^^H j ^, -O-sugar, - CH 2 CH(OH)CH 2 OH, -OCH 2 C0 2 H, -O 2 CCH 2 CH 2 CO 2 H, -CH 2 N=CHN(CH 3 ) 2 , -OR 18 , and -NR 18 ; R j8 is a N-terminal amino acid; Y 2 is hydrogen, -Cl, -F, -OCH 3 , and -CF 3 ; Y- and Y 2 taken together are -OCH 2 O-, -OC(CH 3 ) 2 O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S, or -SCH 2 O-; provided, however, when Z is -CR 15 =CR 16 - (E), and Y 2 , 15, and R 16 are each hydrogen, Y j is not hydrogen, when R 4 is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Y- is -Cl, -F, -Br, -CF 3 , -CN, or -NO 2 , and when R5 is fluorine, Rg, R 7 and R are each hydrogen; or the pharmaceutically acceptable salts thereof. The invention also provides a method for treating a human infected with one or more than one strain of a human immunodeficiency virus (HIV) which comprises administering an effective amount of a compound of formula I wherein R 2 is -CN, -N 3 , -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C j -C 4 alkyl, -Ac, -CO2CH 3 , -CO2C2H5, -phenyl, -PO2-O " cation 4" , -CO-CH(AA)NH 2 , -CO-CgHg-NR n R 12 , and -CO-CgH 6 -CH 2 -NR π R 12 ; AA is -CH 3 , -CH(CH 3 )2, -CH 2 CH(CH 3 ) 2 ,-CH 2 OH, -CH(OH)CH 3 , -CHJCOJH, -CH 2 CH 2 CO 2 H, -(CH2) 4 NH 2 , and -(CH^-NH j ; R j j and R 12 may be the same or different and are hydrogen and C j -C 4 alkyl; Ru and R 12 taken together are moφholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N-(C j -C 4 alky piperazinyl; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen, C j -C 4 alkyl, -(CH^.CN, and -(CH^R^; R 13 is -N(CH3) 2 , -OH, -OPO 3 H, - CH 2 CH(-OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 C(CH2) 2 CO 2 H, -OR 14 , and -NR 14 ; R 14 is a N-terminal amino acid; a is zero to six; b is one to five; A is CH, CH 2 , N, and CHN(CH 3 )2; X is CH, CH 2 , NH, O, and C-R 4 ; R 4 is -CH 3j -OCH 3 , and -OAc; R 5 , Rg, R 7 , and R 8 may be the same or different and are hydrogen and fluorine; W is oxygen and sulfur; Z is a direct bond or a linker selected from the group consisting of -(CO)-, -CH=CH-CH=CH- (all E), -CR 15 =CR 16 - (E or Z), and -CH=C=CH-; R 15 and R j g may be the same or different and are hydrogen and fluorine; Y χ is hydrogen, -Cl, -F, -Br, -CH 3 , -CF 3 , -(CH 2 ) C R 17 , -CHO, -CO 2 CH 3 , -OH, -OCH 3 -OAc, -CN, - 02, -SH, and -SCH 3 ; c is zero to five; R 17 is -CH 2 N(CH 3 ) 2 , -OH, -OPO 3 H, -CH 2 N(C 2 H 5 ) 2 , -O-sugar, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 CCH 2 CH 2 CO 2 H, -OR 18 , or -NKIS; R 18 is an N-terminal amino acid; Y 2 is hydrogen, -Cl, -F, -OCH 3 , and -CF 3 ; Y x and Y 2 taken together can form -OCH 2 O-, -OC^H^O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S-, -SCH 2 O-, and -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, when Z is a direct bond and R 2 is -C(=NOH)N(R 10 )H and R 10 is hydrogen, R 19 is not hydrogen, when Z is a direct bond, Y j is not hydrogen, when Y j is -OCH 3 and Z is a direct bond, at least one of , Rg, R 7 or R 8 is fluorine, when Y j is -CF 3 and Z is direct bond, die connection between positions 3 and 4 is a double bond, when Z is a direct bond, X is not O, when Z is a direct bond, R 2 is not -N 3 , when Z is a direct bond, Y 2 is hydrogen or -F, when A is N, X is C-R 4 and R 4 is -OCH 3 or -OAc and the connection between position 3 and 4 is a double bond, when A is CHN(CH 3 )2, X is CH 2 , when R 4 is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Y l is -Cl, -F, -Br, -CF 3 , -CN, or -NC^, when R 5 is fluorine, Rg, R 7 and Rg are each hydrogen, when Y j and Y 2 taken together are -CH=CR 19 -CH=CH-, Z is a direct bond, and when Y! and Y 2 Uiken together can form -OCH 2 O-, -O CH^O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S-, and -SCH 2 O-, Z is a linker; to a human patient. The preferred compound for this method is l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)- 2-cyano-l ,2-dihydroquinoline. The invention further provides die use of the compounds of me invention and/or their pharmaceutically acceptable salts, hydrates, and solvates for the preparation of pharmaceutical formulations. These formulations are useful to practice the method claimed in this invention. DETAILED DESCRIPTION OF THE INVENTION Generally, the compounds of formula I are preferred. Particularly preferred are the compounds of the invention wherein there is a double bond between A and X, and A is CH. It is preferred that X is CH. It is preferred that Z is -CR 15 =CR 16 - (E), and that R j 5 and R 16 are hydrogen. It is preferred that W is O. It is preferred that R 3 and R5 are hydrogen and Rg R 7 and R 8 are eidier hydrogen or F. It is preferred that R 2 is CN. It is preferred that Y 2 is hydrogen. It is preferred that Y l is Cl or CN, most preferred is where Y t is Cl. It is understood by those skilled in the art that the stereoisomers and enantiomers of the compounds of the invention are included within the scope of the invention. The compounds of the invention are useful as inhibitors of viral reverse transcriptase, an enzyme necessary for human immunodeficiency virus replication, and therefore would be useful in the treatment of disease, such as acquired immune deficiency syndrome (AIDS). The term human retrovirus (HRV) includes human immunodeficiency virus type I (HIV-I), or variant strains thereof, apparent to one skilled in the art, which belong to the same viral families and which create similar physiological effects in humans as HRV. Patients to be treated would be those individuals: 1) infected with one or more than one strain of a human retrovirus as determined by the presence of either measurable viral antibody or antigen in the serum and 2) having either a symptomatic AIDS defining infection such as (a) disseminated histoplasmosis, (b) isopsoriasis, (c) bronchial and pulmonary candidiasis including pneumocystic pneumonia, (d) non-Hodgkin's lymphoma, or (e) Kaposi's sarcoma and being less than sixty years old; or having an absolute CD4 lymphocyte count of less than 500/mm 3 in the peripheral blood. Additionally, persons who show the signs and symptoms of AIDS-related complex (ARC) may be treated with the compounds of this invention. Such signs and symptoms include, but are not limited to, generalized lymph adenopathy, weight loss, anemia, candidiasis, and immunologic abnormalities characteristic of AIDS. Treatment of ARC and AIDS patients would consist of maintaining an inhibitory level of the compound of the invention used according to t is invention in the patient at all times and would continue until the occurrence of a second symptomatic AIDS defining infection indicates alternate therapy is needed. Treatment of asymptomatic patients would typically require lower daily maintenance dosages. In addition, the compounds of the invention may be used in conjunction with other antiviral agents such as AZT. The compounds of the invention, or pharmaceutically acceptable salts, hydrates, and solvates thereof, can be used and administered in practicing the method claimed in this invention. The compounds of the invention may form acid addition salts when reacted with acids of sufficient strength to produce the corresponding salt. In addition, some of the variable substituents are acids and thus form base addition salts when reacted with bases of sufficient strength. Pharmaceutically acceptable salts refers to those salts of the compounds of the invention which would be readily apparent to a manufacturing pharmaceutical chemist to be equivalent to, or better than, the parent compound in properties such as formulation, stability, patient acceptance, and bioavailability. Generally, the pharmaceutically acceptable salts, either acid or base as die case may be, are preferable over the free acid or base since the salt is more water soluble and more crystalline. The pharmaceutically acceptable salts include both inorganic and organic acids and bases. Examples of pharmaceutically acceptable salts include salts of the following acids: methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, tartaric, fumaric, maleic, p-toluenesulfonic, benzenesulfonic, and die like. Examples of pharmaceutically acceptable salts include salts of the following bases: hydroxide, ammonia, tromethamine (THAM), and d e like. Suitable cations include, for example, sodium, potassium, calcium, and magnesium. Those skilled in die art would know how to formulate the compounds used to practice the method claimed in this invention into appropriate pharmaceutical dosage forms. Examples of the dosage forms include oral formulations, such as tablets or capsules, or parenteral formulations, such as sterile solutions. When the compounds used to practice the method claimed in this invention are administered orally, an effective amount is from about 0.2 to about 100 mg per kg per day for asymptomatic patients, and about 1 to about 500 mg per kg per day for ARC and AIDS patients. A typical unit dose for a 70 kg human AIDS patients would be from about 50 mg to 1000 mg, preferably 200 mg to 1000 mg taken one to four times per day. Either solid or fluid dosage forms can be prepared for oral administration. Solid compositions are prepared by mixing the compounds used to practice the method claimed in this invention with conventional ingredients such as talc, magnesium stearate, dicalcium phosphate, magnesium aluminum sili- cate, calcium sulfate, starch, lactose, acacia, methyl cellulose, or functionally similar pharmaceutical diluents and carriers. Capsules are prepared by mixing the compounds used to practice the method claimed in this invention with an inert pharmaceutical diluent and placing d e mixture into an appropriately sized hard gelatin capsule. Soft gelatin capsules are prepared by machine encapsulation of a slurry of the compounds used to practice the method claimed in mis invention with an acceptable inert oil such as vegetable oil or light liquid petrolatum. Syrups are prepared by dissolving d e compounds used to practice the method claimed in this invention in an aqueous vehicle and adding sugar, aromatic flavoring agents and preservatives. Elixirs are prepared using a hydroalcoholic vehicle such as e-thanol, suitable sweeteners such as sugar or saccharin and an aromatic flavoring agent. Suspensions are prepared with an aqueous or organic vehicle and a suspending agent such as acacia, tragacanth, or methyl cellulose. When the compounds used to practice the method claimed in this invention are administered parenterally, it can be given by injection or by intravenous infusion. An effective amount is from about 1 to 100 mg per kg per day. Parenteral solutions are prepared by dissolving the compounds used to practice the method claimed in mis invention in an appropriate solvent and filter sterilizing the solution before placing in a suitable scalable vial or ampule. Parenteral suspensions are prepared in substantially the same way except a sterile suspension vehicle is used and the compounds used to practice the method claimed in this invention are sterilized with ethylene oxide, suitable gas or oύier methods known in the art, before it is suspended in die vehicle. The exact route of administration, dose, or frequency of administration would be readily determined by one skilled in die art and is dependent on die particular compound of the invention being used, and on die age, weight, general physical condition, odier medication the individual is taking, or other clinical symptoms specific to the patient to be treated. Terms used in this specification and claims have the following definitions: "AIDS" means acquired immune deficiency syndrome. "ARC" means AIDS-related complex. "E or Z" designates stereochemistry around a double bond. The two groups attached to each atom of the double bond are assigned priorities according to die Prelog-Cahn-Ingold system. "E" refers to an arrangement in which d e two higher priority or two lower priority groups are on the opposite sides of die double bond. "Z" refers to an arrangement in which the two higher priority groups are on the same side of the double bond. "Phenyl" means -C 6 H 5 "N-terminal .amino acid" means a naturally occurring amino acid, and synthetic derivatives thereof, in which the amino group is free, i.e., the amino acid is linked via die carboxyl group to form either an ester or an amide. "-Ac" means -C(O)CH 3 ; "-OAc" means -OC(O)CH 3 . "O-sugar" means a hexose or pentose monosaccharide linked at the 2-hydroxyl group. "-CO 2 -" or "-C(O)O-" designates an ester linked via the carbon. "-O 2 C-" or "-OC(O)-" also designates an ester, with the linkage via the oxygen. "-CC^H" designates a carboxylic acid. "-CH=CR 19 -CH=CH-" designates a carbon chain linking Y! and Y 2 where (Y j end) -CH=CR 19 -CH=CH- (Y 2 end). Throughout the disclosure and claims, common shorthand chemical terms are used. The carbon atom content of the various hydrocarbon-contain ~ xg moieties is indicated by designating die minimum and maximum number of carbon atoms in the moiety, i.e. C m -C π indicates a moiety of integer "m" to the integer "n" carbon atoms, inclusive and includes the isomeric forms. For example, C j -Cg alkyl refers to an alkyl of one to six carbons, inclusive, including the isomeric forms. Chemical formulas, or portions thereof, drawn in a linear fashion may use the symbol "-" to represent a single chemical bond between atoms in the linear chain. Likewise, the symbol " = " represents a double bond, and " »" a triple bond, between atoms in the chain. In the structural formulas the symbol " — " represents a bond between two atoms which may be a single or a double bond; die symbol " " represents a bond which may or may not be present, and if present, is a single bond. Temperatures are in degrees Celsius. The letter "h" means hours. "TLC" means thin layer chromatography. MS refers to mass spectrometry. MS data are expressed as m/e or mass/change unit. Synthesis of Representative Compounds In preparative methods that follow, the compounds of die invention are synthesized following techniques which are known, or readily acquired, by one skilled in die art. Examples of such techniques are: F.D. Popp, "Reissert Compounds and Related N-acyldihydroquinolines" in Quinolines, Part π, Ed. G. Jones, (1982) p. 353-372, is a general review covering the synthesis and reactions of Reissert compounds. This review specifically describes die synthesis of l-(4- chlorobenzoyl)-2-cyano-l,2-dihydroquinoline, l-(4-fluorobenzoyl)-2-cyano-l,2- dihydroquinoline, l-(4-methoxybenzoyl)-2-cyano-l,2-dihydroquinoline, l-(4-toluoyI)-2-cyano- 1 ,2-dihydroquinoline, l-(4-nitrobenzoyl)-2-cyano-l,2-dihydroquinoline, l-(2-naphthoyl)-2- cyano-l,2-dihydroquinoline, and l-(l-oxo-3-phenyl-2-propenyl)-2-cyano-l,2-dihydroquinoline. F.D. Popp, W. Blount and P. Melvin, ∑. Qrg. Chem.. 26, 4930 (1961), describes the methyl eπe chloride/water method for synthesizing Reissert Compounds. S. Ruchirawat, N. Phadungkul, M. Chuankamnerdkarn, and C. Thebtaranonth, Heterocycles. 6, No. 1, 43 (1977), describes the trimethylsilyl cyanide method of syndiesizing Reissert compounds. M. Rozwadowska, Roczniki Chemii. 51, 2321 (1977), describes hydrogenation of dihydroquinoline Reissert compounds to tetrahydroquinolines. L. Walters, M. Siegel, and R. Cook, ∑. Heterocyclic Chem.. 5, 577 (1968), describes synthesis of amidoximes, also called carboxamidamides, via addition of hydroxylamine to a Reissert compound. H. Bartsch, O. Schwarz, and G. Neubauer, Heterocycles. 24, 3483 (1986), describes die synthesis of a benzoxazine Reissert compound. F. Elroy and R. Lenaers, "The Chemistry of Amidoximes and Related Compounds," Chem. Rev. 155 (1962), describes syndiesis and reactions of amidoximes. Uff, B.C., Budhram, R.S., Consterdine, M.F., Hicks, J.K., and Slingsby, B.P., ∑. Chem. Soc. Perkins Trans I (18):2018-22 (1977), describes syndiesis of l-(4- methoxybenzoyl)-2-cyano-4-methyl- 1 ,2-dihydroquinoline. F.D. Popp and A. Soto, ∑. Chem. Soc. 1760 (1963), describes the synthesis of l-(4- fluorobenzoyl)-2-cyano- 1 ,2-dihydroquinoline. All starting materials are known and are commercially available, or are readily prepared from known or readily available materials. The syndiesis of compounds of die invention proceed, generally, as oudined below and, more specifically, in die representative examples that follow. The synthesis of the dihydro- and tetrahydroquinolines, the dihydroquinazolines and die dihydroquinoxalines are oudined in Chart A, the tetrahydrobenzoxazines in Chart B, and the amidoxime compounds of die invention in Chart C. In the Charts the l-(benzoyl) or l-(άnnamoyl) substituents are designated "R", and the halide of the acid halide is designated "X". The examples that follow are illustrative and not limitations of the preceding disclosure. The conditions described here and in die examples for the synthesis and purification of the compounds of die invention may be altered depending on the choice of reactants and solvents, the batch size, the degree to which the reaction is to be carried to completion, and odier factors of concern to the chemist. Procedure for preparation of Reissert compounds (Chart A). There are numerous techniques available for the synthesis of Reissert compounds from quinoline. Among these are preparation in aqueous potassium cyanide, potassium cyanide in a dimethylformamide-water mixture, liquid sulphur dioxide as a solvent, anhydrous benzene- liquid hydrogen cyanide, and trimethylsilyl cyanide-aluminum chloride in methylene chloride. See, F.D. Popp, "Reissert Compounds and Related N-acyldihydroquinolines" in Quinolines, Part II, Ed. G. Jones, (1982) p. 353-372. We prefer the me ylene chloride-trimediylsilyl cyanide system. Referring now to Chart A, one equivalent (1 eq.) of the quinoline (Chart A fig. 1), quinazoline (Chart A, fig. 4), quinoxaline (Chart A, fig. 5), or substituted forms thereof, is dissolved in dichloromethane or acetonitrile to a concentration of 0.4-0.5 M. An acid halide, preferably chloride, (1.5-2 eq.), Lewis acid, preferably aluminum trichloride (.anhydrous, 0.05 eq.) and trimethylsilyl cyanide (1.5-2 eq.) are added while stirring. A thio-acid halide is substituted when die corresponding thio-Reissert compound is desired. Thio-acid halides are synthesized following known procedures, for example, R. Mayer and S. Scheidiauer, J. Heterocyclic Chem. 16, 1589 (1977). The Reissert reaction is carried out under ambient temperature conditions, e.g. 23-27 degrees, or refluxing acetonitrile for 8-substituted compounds, for a time sufficient to effect as complete a reaction as possible, e.g. from 0.5 to 48 hours. The products of die reaction (Chart A, fig. 2) are followed by TLC using solvent systems known in the art. Upon completion, the reaction is concentrated in vacuo and then placed on a silica gel column and eluted under flash chromatography conditions. The product is recrystallized from a low boiling point aliphatic alcohol, preferably 95% ethanol, or ethylacetate/hexane. When a tetrahydroquinoline product is desired, die dihydroquinoline (Chart A, fig. 2) is dissolved in alcohol, preferably 95% ethanol, and reduced by hydrogenation in die presence of platinum. The reaction is followed and die product (Chart A, fig. 3) recrystallized as oudined above. Preparation 1 6,7-difluoroquinoline Sodium 3-nitrobenzensulphonate (27.25 g, 1.25 eq.), followed by glycerol (25.50 g, 20.22 ml, 2.86 equiv.), and aqueous sulphuric acid (80% w/w, 81 ml) are placed in a 1 L. diree-necked flask. With stirring, 3,4-difluoroaniline (12.50 g, 9.60 ml, 1 eq.) is slowly added and then heated under gentle reflux in an oil bath at 175 °C for 5 hours. The reaction mixture is cooled to room temperature and treated widi aqueous sodium nitrite (25% w/w, 55 ml) from a dropping funnel. The mixture is subjected to steam-distillation. The yellowish aqueous distillate is discarded. The reaction product is cooled in an ice bath, made strongly alkaline, i.e. pH 9-12, by the cautious addition of aqueous sodium hydroxide (50% w/w), and again subjected to steam distillation. A colorless solid formed in both d e condenser and receiver. Extraction with ethyl acetate, drying over sodium sulphate, and removal of die solvent in the rotary evaporator at 35°C. under house vacuum gave a solid (13.20 g) TLC in hexane-methanol (1:6 v/v) showed the presence of a major and a minor product. Direct crystallization gave 6,7- difluoroquinoline (9.25 g) m.p. 112-113°C. The mother liquors contain the minor 5,6- difluoro-isomer. Preparation 2 6,8-difluoroquinoline 6,8-difluoroquinoline is synthesized by substituting 2,4-difluoroaniline for 3,4- difluoroaniline in Preparation 1. The remaining procedure and purification are substantially unchanged. Preparation 3 7,8 difluoroquinoline 7,8-difluoroquinoline is syndiesized by substituting 2,3-difluoroaniline for the 3,4- difluoroaniline in Preparation 1. The remainder of die procedure and purification are substantially unchanged. Preparation 4 4-cyanocinnamic acid 4-cyanobenzaldehyde (1 eq.), malonic acid (1 eq.), pyridine (0.8 M), and piperidine (1 ml/10 ml pyridine) are heated at reflux for 24 h. or until carbon dioxide is no longer evolved. The mixture is evaporated to dryness in vacuo. The residue is redissolved in water and die pH adjusted to 10 using concentrated ammonium hydroxide. The mixture is filtered through celite and die filter rinsed widi water. The pH of the filtrate is adjusted to 2 using IN hydrochloric acid. Chilling precipitates solids which are collected, dissolved in acetone and 95% ethanol, and evaporated in vacuo until solids form. Chilling produces crystalline compound (4- cyanocinnamic acid). Preparation 5 4-cyanocinnamoyl chloride 4-Cyanocinnamic acid (Preparation 4, 1 eq.) is dissolved in methylene chloride at a concentration of 0.5 M. Oxalyl chloride (1 eq.) is added and the mixture chilled to 0°C. DMF (0.5 eq.) is added, die mixture stirred at 0°C for 0.5 h. warmed to ambient temperature, and stirred an additional 2 hours. Evaporation in vacuo yields 4-cyanocinnamoyl chloride. Example la l-(4-bromobenzoyl)-2-cyano-l ,2-dihydroquinoline Quinoline (0.104 g, 0.8 mmol) is dissolved in 0.5 ml of methylene chloride. 88 μL of trimethylsilylcyanide is added at ambient temperature. 4-Bromobenzoyl chloride (0.25 g.) is dissolved in 0.5 mL of methylene chloride is added following 5 mg of aluminum trichloride. After 40 min. the reaction is filtered through a pad of silica gel and the pad is washed with 20 mL of memylene chloride. The combined filtrates are washed first with 10 mL of water, men with 10 mL of saturated aqueous sodium bicarbonate and finally 5 mL of water. The organic layers are concentrated in vacuo to afford an oil which is dissolved in 4 ml of 95 percent ethanol. This is evaporated to 2.5 mL and cooled at 0°C for 30 min. The crystals are collected and dried in a vacuum oven to afford 85 mg of l-(4-bromobenzoyl)-2-cyano-l,2- dihydroquinoline (m.p. 149-151°C). The mother liquor is evaporated and triturated with 1 mL of 95 percent ethanol. The crystals formed are collected and dried to afford 31 mg of a second crop. In an analogous manner, the following compounds are synthesized using d e designated acid chloride. Example lb l-(4-fluorobenzoyl)-2-cyano-l ,2-dihydroquinoline Following the procedure of Example la, 4-fluorobenzoyl chloride is used as the acid chloride and die product, l-(4-fluorobenzoyl)-2-cyano-l,2-dihydroquinoline, has a m.p. 114- 116°C. Example 2 1 -(4-trifluoromethylbenzoyl)-2-cyano- 1 ,2-dihydroquinoline Following die procedure of Example la, 4-trifluoromethylbenzoyl chloride is used as the acid chloride. The product, l-(4-trifluoromethylbenzoyl)-2-cyano-l,2-dihydroquinoline, has a m.p. 135-136°C. Example 3 l-E-(l-oxo-3-phenyl-2-propenyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example la, 1-E-crnamoyl chloride is used as the acid chloride. The product, l-E-(l-oxo-3-phenyl-2-propenyl)-2-cyano-l,2-dihydroquinoline, has m.p. 149-150°C. Example 4 l-E-(3-(4-trifluoromethylphenyl)-l-oxo-2-propenyl)-2-cy.ano-l ,2- dihydroquinoline Following the procedure of Example la, E-4-trifluoromethylcinnamoyl chloride is used as the acid chloride. The product, l-E-(3-(4-trifluoromedιylphenyl)-l-oxo-2-propenyl)-2-cyano- 1,2-dihydroquinoline, has a m.p. 172-173°C. Example 5 l-(4-carbomethoxybenzoyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example 1, 4-carbomethoxybenzoyl chloride is used as the acid chloride. The product, l-(4-carbomethoxybenzoyl)-2-cyano-l,2-dihydroquinoline, has a m.p. 165-166°C. Example 6 l-(4-cyanobenzoyl)-2-cyano-l ,2-dihydroquinoline Following die procedure of Example la, 4-cyanobenzoyl chloride is used as the acid chloride. The product, l-(4-cyanobenzoyl)-2-cyano-l,2-dihydroquinoline, has a m.p. 154- 155°C. Example 7 l-E-(3-(4-chIorophenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example la, E-4-chlorocinnamoyl chloride is used as the acid chloride. The product, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-cyano-l,2- dihydroquinoline has a m.p. 166-167°C. Example 8 l-E-(3-(4-fluorophenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example la, E-4-fluorocinnamoyl chloride is used as the acid chloride. The product, l-E-(3-(4-fluorophenyl)-l-oxo-2-prophenyl)-2-cyano-l,2- dihydroquinoline has a m.p. 142-143°C. Example 9 1 -E-(2-fluoro- 1 -oxo-3-phenyl-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline Following the procedure of Example la, E-α-fluorocinnamoyl chloride is used as the acid chloride. The product, l-E-(2-fluoro-l-oxo-3-phenyl-2-propenyl)-2-cyano-l,2- dihydroquinoline, has a m.p. 152-153°C. Example 10 l-E-(3-(3,4-dichlorophenyl)-l- xo-2-propenyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example la, E-3,4-dichlorocinnamoyl chloride is used as the acid chloride. The product, l-E-(3,4-dichlorophenyl-l-oxo-2-propenyl)-2-cyano-l,2- dihydroquinoline , has a m.p. 152-153°C. Example 11 l-E-(3-(4-cyanophenyl)-l-oxo-2-propenyI)-2-cyano-l,2→lihydroquinoIine Following the procedure of Example la, E-4-cyanocinnamoyI chloride (Preparation 5) is used as die acid chloride. The product, l-E-(3-(4-cyanophenyl)-l-oxo-2-propenyl)-2-cyano- 1,2-dihydroquinolinehas a m.p. 176°C. Example 12 l-E-(3-(3,4-memylenedioxyphenyI)-l-oxo-2-propenyl)-2-cyano-l,2- dihydroquinoline Following die procedure of Example la, E-3,4-medιylenedioxyciπnamoyl chloride is used as die acid chloride. The product, l-E-(3-(3,4-medιylenedioxyphenyl)-l-oxo-2-propenyl 2- cyano-l,2-dihydroquinoline , has a m.p. 176-177°C. Example 13 l-E-(3-(4-methoxyphenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example la, E-4-methoxycinnamoyl chloride is used as the acid chloride. The product is l-E-(3-(4-methoxyphenyl)-l-oxo-2-propenyI)-2-cyano-l,2- dihydroquinoline. Calcd.: C,75.93; H, 5.10; N, 8.85 Found: C, 75.74; H, 5.31; N, 8.86 Example 14a l-E-(3-(4-acetoxyphenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example la, E-4-acetoxycinnamoyl chloride is used as the acid chloride. The product is l-E-(3-(4-acetoxyphenyl)-l-oxo-2-propenyl)-2-cyano-l,2- dihydroquinoline. Calcd.: C, 73.24; H, 4.68; N, 8.13 Found: C, 72.94; H, 4.51; N, 7.99 Example 14b 1 -E-(3-(4-carbomethoxybenzoyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2- dihydroquinoline Following d e procedure of Example la, E-4-carbomethoxycinnamoyl chloride is used as the acid chloride. The product, l-E-(3-(4-carbomethoxybenzoyl)-l-oxo-2-propenyl)-2-cyano- 1,2-dihydroquinoIine, has a m.p. 168-170PC. Example 15 1 -E-(3-(4-methylphenyI)- 1 -oxo-2-trans-propenyl)-2-cyano- 1 ,2-dihydroquinol ine Following the procedure of Example la, E-(4-medιylcinnamoyl chloride) is used as the acid chloride. The product is l-E-(3-(4-methylphenyl)-l-oxo-2-propenyl)-2-cyano-l,2- dihydroquinoline. Calcd.: C, 79.98; H, 5.37; N, 9.33 Found: C, 79.54; H, 5.40; N, 9.17 Example 16 l-(2-napthoyl)-2-cyano-l,2- lihydroquinoline Following the procedure of Example la, 2 -napdioyl chloride is used as die acid chloride. The product, l-(2-napthoyl)-2-cyano-l,2-dihydroquinoline, has a m.p. 185-186°C. Example 17 1 -(4-chlorobenzoyl)-2-cyano-4-methyl- 1 ,2-dihydroquinoline Following die procedure of Example la, 4-methylquinoline is substituted for quinoline and 4-chlorobenzoyl chloride is used as die acid chloride. The product, l-(4-chlorobenzoyl)-2- cyano-4-methyl-l,2-dihydroquinoline, has a m.p. 173-174°C. Calcd. for C 18 H 13 ClN 2 O: C, 70.02; H, 4.24; N, 9.08; Cl, 11.48. Found: C, 69.95; ;H, 4.28; N, 8.90; Cl, 11.45. Example 18 l-(4-chlorobenzoyl)-2-cyano-5-fluoro-l,2-dihydroquinoline Following the procedure of Example la, 5-fluoroquinoline is substituted for quinoline and 4-chlorobenzoyl chloride is used as the acid chloride. The product, l-(4-chlorobenzoyl)-2- SUBSTITUTE SHEET cyano-5-fluoro-l,2-dihydroquinoline, has a m.p. 144-14a5°C. Calcd. for C 17 H 10 C1FN 2 O: C, 65.29; H, 3.22; N, 8.96; Cl, 11.34; F, 6.08. Found: C, 65.37; H, 3.24; N, 9.03; Cl; 11.32; F, 6.47. Example 19a 1 -(4-chlorobenzoyl)-2-cyano-6-fluoro- 1 , 2-dihydroquinoline Following the procedure of Example la, 6-fluoroquinoline is substituted for quinoline and 4-chlorobenzoyl chloride is used as the acid chloride. The product, l-(4-chlorobenzoyl)-2- cyanoH5-fluoro-l,2-dihydroquinoIine, has a m.p. 147-148°C. Calcd. for C I7 H 10 C1FN 2 O: C, 65.29; H, 3.22; N, 8.96; Cl, 11.34; F, 6.08. Found: C, 65.18; H, 3.27; N, 8.87; Cl, 11.09; F, 6.36 Example 19b l-(4-chlorobenzoyl)-6-fluoro-2-cyano-l,4-dihydroquinoline The product of Example 19a is subjected to reverse-phase HPLC separation (isocratic 40% THF/60% water mobile phase). Pure l-(4-chlorobenzoyl)-6-fluoro-2-cyano-l,4- dihydroquinoline is isolated (m.p. 144-150°C). Example 20 l-(4-chlorobenzoyl)-2-cyano-7-fluoro-l ,2-dihydroquinoline Following die procedure of Example la, 7-fluoroquinoline is substituted for quinoline and 4-chlorobenzoyl chloride is used as die acid chloride. The product, l-(4-chlorobenzoyl)-2- cyano-7-fluoro-l,2-dihydroquinoline, has a m.p. 174-175°C. Calcd. for C 17 H 10 C1FN 2 O: C, 65.29; H, 3.22; N, 8.96; Cl, 11.34; F, 6.08. Found: C, 65.23; H, 3.27; N, 8.98; Cl, 10.99; F, 6.19. Example 21 l-(4-chlorobenzoyl)-2-cyano-8-fluoro-l, 2-dihydroquinoline Following die procedure of Example la, 8-fluoroquinoline is substituted for quinoline and 4-chlorobenzoyl chloride is used as the acid chloride in acetonitrile solvent and the solution refluxed as described above. The product, l-(4-chlorobenzoyl)-2-cyano-8-fluoro-l,2- dihydroquinoline, has a m.p. 156-157°C. Calcd. for C 17 H 10 CIFN 2 O: C, 65.29; H, 3.22; N, 8.96; Cl, 11.34; F, 6.08. Found: C, 65.36; H, 3.23; N, 8.92; Cl, 11.16: F, 6.02. Example 22 l-(4-methoxybenzoyl)-2-cyano-6,7-difluoro-l,2-dihydroquinoline Following the procedure of Example la, 6,7-difluoroquinoline (Preparation 1) is substituted for quinoline and 4-methoxybenzoyl chloride is used as the acid chloride, m.p. 139- 140°C. Calcd. for C 18 H 12 F 2 N 2 O 2 : C, 66.25; H, 3.71; N, 8.59; F, 11.65. Found: C, 66.65; H, 3.73; N, 8.47; F, 12.09. Example 23 l-(4-chlorobenzoyl)-2-cyano-l ,4-dihydroquinoxaline Following the procedure of Example la, quinoxaline is used in place of quinoline and 4- chlorobenzoyl chloride is die acid halide. The product, l-(4-chlorobenzoyI)-2-cyano-l,4- dihydroquinoxaline, has a m.p. 231-232°C. Calcd. for C 16 H 10 C1N 3 O: C, 64.98; H, 3.40; N, 14.21. Found: C, 65.05; H, 3.55; N, 14.30. Example 24 l-(4-chlorobenzoyl)-2-cyano-6,7-difluoro-l ,2-dihydroquinoline Following the procedure of Example la, 6,7-difluoroquinoline (Preparation 1) is the quionoline and 4-chlorobenzoyl chloride is die acid halide. The product, l-(4-chlorobenzoyl)-2- cyano-6,7-difluoro-l, 2-dihydroquinoline, has a m.p. 184-185°C. Calcd for C l7 H 9 aF 2 li 2 0: C, 61.74; H, 2.74; N, 8.47; Cl, 10.72; F, 11.49. Found: C, 61.59; H, 2.82; N, 8.48; Cl, 10.6; F, 11.37. Example 25 1 -(4-chlorobenzoyl)-6,8-difluoro-2-cyano-l ,2-dihydroquinoline Following the procedure of Example la, 6,8-difluoroquinoline (Preparation 2) is substituted for quinoline and 4-chlorobenzoyl chloride is used as the acid chloride. The product, l-(4-chlorobenzoyl)-6,8-difluoro-2-cyano-l, 2-dihydroquinoline, has a m.p. 164-165°C. Example 26 l-(4-chlorobenzoyl)-7,8-difluoro-2-cyano-l ,2-dihydroquinoline Following the procedure of Example la, 7,8-difluoroquinoline (Preparation 3) is substituted for quinoline and 4-chlorobenzoyl chloride is used as the acid chloride m.p. 154- 155°C. Calcd: C, 72.72; H, 4.27; N, 8.48. Found: C, 72,54; H, 4.35; N, 8.44. Example 27 l-E-(3-(4-bromophenyl)-l-oxo-2-propenyl)-2-cyano-l ,2-dihydroquinoline Following the procedure of Example la, E-4-bromocinnamoyl chloride is substituted for the acid halide. The product, l-E-(3-(4-bromophenyl)-l-oxo-2-propenyl)-2-cyano-l,2- dihydroquinoline, has a m.p. 175-177°C. Example 28 l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-cyano-6,7-difluoro-l,2- dihydroquinoline Following the procedure of Example la, 6,7-difluoroquinoline (Preparation 1) is substituted for quinoline and 4-chlorocinnamoyl chloride is substituted for the acid halide. The product, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-cyano-6,7-difluoro-l,2-dihydroquinoline, has a m.p. 97-98°C. Example 29 1 -E-(3-(4-fluorophenyl)- 1 -oxo-2-propenyl)-2-cyano-6,7-difluoro- 1 ,2- dihydroquinoline Following the procedure of Example la, 6,7-difluoroquinoline (Preparation 1) is substituted for quinoline and 4-fluorocinnamoyl chloride is used as the acid chloride. The product, l-E-(3-(4-fluorophenyI)-l-oxo-2-propenyl)-2-cvano-6,7-difluoro-l,2-dihydroquinoline, has a m.p. 131-132°C. Example 30a l-(4-chlorobenzoyl)-2-cyano-6,7,8-trifluoro-l, 2-dihydroquinoline Following the procedure of Example la, 6,7,8-trifluoroquinoline is substituted for TIT H quinoline and 4-chlorocinnamoyl chloride is substituted from the acid chloride. The product, 1- (4-chlorobenzoyI)-2-cyano-6,7,8-trifluoro-l, 2-dihydroquinoline, has a m.p. 159-160PC. Example 30b l-E,E-(l-oxo-2,4-pentadienyl-5-phenyl)-2-cyano-l,2-dihydroquinoline Following the procedure of Example la, styryl acrolyl chloride is substituted for the acid halide. The tide product is obtained. l E NMR (300 MH 2 , CDC1 3 ): d 6.04 (dd, J = 11,15 Hz, 1H), 6.35 (d, J=15 Hz, 1H), 6.37 (dd, J= 1,6 Hz, 1H), 6.77 (d, J= 9Hz, 1H), 6.82 (dd, J=ll,15 Hz, 1H), 7.22-7.37 (m, 7H), 7.43 (m, 2H), 7.62 (dd, J= 11,15 Hz, 1H). Example 31 I-(4-trifluorobenzoyl)-2-cyano-3- iimethylamino-l,2,3,4-tetrahydroquinoline To 500 mg (1.52 mmol) of l-(4-trifluoromethylbenzoyl)-2-cyano-l, 2-dihydroquinoline is added 20 ml of methylene dichloride and 3 ml of anhydrous dimethylamine (the dimediylamine is cooled to below -20°C before carefully opening the sealed botde). The reaction is allowed to stir at ambient temperature for 48 h., filtered and the resulting methylene chloride solution evaporated to dryness. The residue is distributed between methylene chloride and water, and die organic phase washed twice with water. The organic phase is dried over anhydrous sodium sulfate, filtered, and evaporated to dryness to give crude product. The crude product is chromatographed using 35 percent ethyl acetate in hexane to give l-(4-trifluorobenzoyl)-2- cyano-3-dimethylamino-l,2,3,4-tetrahydroquinoIine which slowly crystallizes upon standing (m.p. 104-106°C). Example 32 l-(4-chlorobenzoyl)-2-cyano-l,2,3,4-tetrahydroquinoline. To one gr-am of l-(4-chlorobenzoyl)-2-cyano-l ,2-dihydroquinoline (3.4 mmol) in 100 ml of 95% ethanol is added 0.10 g of platinum oxide. The reduction reaction proceeds under hydrogen at atmospheric pressure 4 hours. The reaction is followed by TLC (35% ethyl acetate hexane). The reaction is filtered and d e resulting ethanol solution is concentrated in vacuo; the crude solid is recrystallized from 5 ml of absolute edianol to give the tetrahydroquinoIine (l-(4-chlorobenzoyl)-2-cyano-l,2,3,4-tetrahydroquinoline, 0.21 mg, m.p. 134-135°C). Calcd.: C, 68.78, H, 4.41; N, 9.44, Cl, 11.94. Found: C, 68.66; H, 4.81; N, 9.16; Cl, 11.71. Example 33 l-Z-(l-oxo-3-phenyl-2-propenyl)-2-cyano-l,2-dihydroquinoline a) Phenylpropiolic acid (K&K Chemicals, 1.05 g, 7.2 mmol) is dissolved in 14 ml of methylene chloride and cooled to 0°C. Oxalyl chloride (0.63 ml) and dimediylformamide (140 μl) are added. The reaction is stirred at 0°C for 30 min., then warmed to ambient temperature and stirred an additional 3 hours. The reaction is concentrated in vacuo and further dried in vacuo for 3 h. at ambient temperature. Quinoline (0.57 ml, 4.8 mmol) is dissolved in 14 ml of methylene chloride and 0.42 ml of trimethylsilylcyanide is added. This solution is added to die phenylpropiolic acid chloride prepared above. Aluminum trichloride (catalytic, 5 ol percent) is added and die reaction is stirred overnight at ambient temperature. The reaction is filtered through a plug of silica gel and washed wid 75 ml of methylene chloride. The organics are washed wid saturated aqueous sodium bicarbonate and evaporated in vacuo. Purification by flash column chromatography (25 percent ethyl acetate/hexane) provides 600 mg of the desired product. b) The above product (200 mg) is dissolved in 7 ml of methanol and 22.6 mg of palladium on calcium carbonate poisoned wid lead (5% palladium, Aldrich) and 9 mg of quinoline is added. The mixture is hydrogenated at 18 psi for 7.5 hours. Filtration of the reaction and concentration in vacuo affords an oil which is dissolved in 95 percent ethanol and chilled at 5°C for 20 hours. The crystalline product is collected to provide l-(l-oxo-3-phenyl- 2-propenyl)-2-cyano- 1 ,2-dihydroquinol ine. Calcd.: C, 79,70; H, 4.93; N, 9.79. Found: C, 79.31; H, 5.01; N, 9.56. Procedure for preparation of benzoxazines (Chart B) Referring now to Chart B, figure 1, l-(o-aminophenoxy)-2,2-diethoxyethane (1 eq.) is prepared following the procedure of F. Choiccara et al., Tetrahedron 32, 1407 (1976). The diedioxyed ane is dissolved in, preferably ether, (0.1-0.3 M) and ethyl diisopropylamine (1-1.2 eq.) is added. The reactants are cooled to O° C and one equivalent of the appropriate cinnamoyl acid halide, preferably substituted cinnamoyl acid chloride, is added dropwise. The reaction is allowed to proceed for a time sufficient to allow as complete a reaction as possible, e.g. 10 min. to 1 hour. The reactants are added to saturated sodium bicarbonate and extracted widi methylene chloride. The organic layers are combined, washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo. The amide product (Chart B, fig. 2) is purified using flash chromatography in ethyl acetate/hexanes. The amide (Chart B. fig. 2) (1 eq.) is dissolved in methylene chloride (0.4-0.5M) and die reaction cooled to -2CPC. An acid, preferably boron trifluoride etherate, (1-1.2 eq.) is added and the reaction mixture is stirred and slowly warmed to ambient temperatures. Stirring continues for from 12 to 20 hours. The mixture is diluted with methylene chloride, washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, and concentrated in vacuo. The product, a substituted 3,4-dihydro-3-ethoxy-2H-l,4-benzoxazine (Chart B, fig. 3), is purified by flash chromatography using a chloroform medianol solvent. The benzoxazine (Chart B, fig. 3, 1 eq.) is dissolved in methylene chloride (0.1-0.2M) and 1 eq. (each) of azidotrimed ylsilane and boron trifluoride etherate is added. The reaction is stirred at ambient temperature for 3-24 h., diluted with methylene chloride, washed widi saturated sodium bicarbonate and again with saturated sodium chloride, dried over sodium sulfate, and concentrated in vacuo. Purification by flash chromatography in ethylacetate/hexane provides a substituted 3,4-dihydro-2H-l,4-dihydrobenzoxazine-3-azide (Chart B, fig. 4). Further purification is accomplished by recrystallization in ethylene/hexane. Example 34 4-(p-chlorocinnamoyI)-3,4-dihydro-2H-l ,4-benzoxazine-3-azide a) 2-(4-chIorocinnamidinyI)phenoxy-l,l-diethoxyethane 1.24 g of l-(o-aminophenoxy)-2,2-diedιoxyedιane (4.85 mmol), prepared following the procedure of F Chioccara, F. Prota, R.H. Thompson, Tetrahedron 32, 1407 (1976), is dissolved in 40 ml of ether and ethyl diisopropylamine (5.82 mmol, 0.75 g) is added. The reaction is cooled to O°C. p-Chlorocinnamoyl chloride (4.85 mmol) dissolved in 10 ml of ether is added dropwise. After 10 min. of stirring, the reaction is poured into saturated aqueous sodium bicarbonate and extracted widi mediylene chloride. The organic layers are combined, washed widi water, dried over anhydrous sodium sulfate, and concentrated in vacuo. Purification via flash column chromatography (200 g silica gel, 10% ethyl acetate/hexane) provides 2-(2-chlorocinnamidinyl)phenoxy)-l, 1-diethoxyedιane. b) 4-(p-chlorocinnamoyl)-3,4-dihydro-3-ethoxy-2H-l,4-benzoxazine 2-(2-(p-Chlorocinnamidinyl)phenoxy-l,l-diethoxyedιane (l mmol), synthesized above, is dissolved in 2 ml of methylene chloride and die reaction is cooled to -20°C. Boron trifluoride ed erate (1.2 mmol) is added, die reaction allowed to slowly warm to room temperature over approximately 2 hours and is then stirred overnight. The mixture is diluted with methylene chloride, washed widi saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, and concentrated in vacuo. Purification by flash column chromatography (100 g silica gel, 100% chloroform) provides 4-φ-chlorocinnamoyl)-3,4-dihydro-3-ethoxy-2H-l,4- benzoxazine. c) 4-φ-chlorocinnamoyl)-3,4-dihydro-2H-l,4-benzoxazine 3-azide 4-(p-ChlorocinnamoyI)-3,4-dihydro-3-ethoxy-2H-l,4-benzoxazine (1 mmol) synthesized in step (b) is dissolved in 7 ml of methylene chloride. Azidotrimethylsilane (1 mmol) and boron trifluoride etherate (1 mmol) are added. After stirring about 3 hours at room temperature, die reaction is diluted widi mediylene chloride, washed widi saturated sodium bicarbonate, saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. Purification by flash column chromatography (10% ethyl acetate/hexane) provides product which is recrystallized from ethyl acetate/hexane to afford die desired product (4-(p- chlorocinnamoyl)-3 ,4-dihydro-2H- 1 ,4-benzoxazine-3-azide) . Procedure for preparation of amidoximes (Chart Q. Referring now to Chart C, figure 1, the Reissert compound (0.68 eq.) is dissolved in meώanol at 30 to 50°C and slowly added to hydroxylamine in medianol at (PC. The hydroxylamine is prepared by adding sodium me oxide (10 eq.) to hydroxylamine hydrochloride (1 eq.) in methanol and then filtering. The Reissert-hydroxylamine reaction is allowed to warm to room temperature while stirring. It is then heated from 3(PC to reflux for 1 to 24 hours. The reaction mixture is cooled to room temperature, diluted widi chloroform, washed widi saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. The product (Chart C, fig. 2) is recrystallized from aqueous (95%) methanol. As an alternative procedure we use die following: Hydroxylamine hydrochloride (1 eq.) is added to a stirred mixture of 1 eq. sodium carbonate in 50 percent aqueous ethanol (0.6-0.8M). The reaction is diluted to 0.06-0.08M with absolute ethanol. Then 0.8 eq. of the desired Reissert compound is added and the reaction is heated at from 50°C to reflux temperature under nitrogen for 2.5 to 24 hours. The reaction poured is mixed into ice water and extracted widi ethyl acetate or butanol. The organics are concentrated in vacuo, dissolved in ethanol, and chilled. The solid product is collected and dried. The pharmacological salt of the amidoxime may be synthesized by use of an appropriate acid. Examples of such salts include hydrochloride, hydrobromide, fumarate, maleate, succinate, citrate, tosylate, and mesylate. Example 35 1 -(4-chlorobenzoyl)-2-carboximidamide- 1 ,2-dihydroquinoline l-(4-chlorobenzoyl)-2-cyano-l,2-dihydroquinoline (0.2g, 0.68 mmol, see Popp, cited above) is dissolved in warm methanol and added to a solution of hydroxylamine in methanol. The hydroxylamine is prepared by the addition of sodium methoxide (0.232 ml of 25% w/w solution in methanol, 1 mmol) to 70 mg of hydroxylamine hydrochloride (1 mmol) in methanol followed by filtration to remove precipitate. The Reissert-hydroxylamine reaction is stirred at ambient temperature for 3 h and subsequendy heated to 40°C for 1 hour. The mixture is evaporated to dryness, dissolved in 2 ml medianol, one drop of water added, and chilled to 5°C. The solids are collected and washed widi methanol to afford l-(4-chlorobenzoyl)-2- carboximidamide-l,2-dihydroquinoline, m.p. 160-161°C. In an analogous manner the following are synthesized by substituting the appropriate Reissert compound. Example 36a 1 -E-(3-(4-bromophenyl)- 1 -oxo-2-propenyl)-2-carboximidamide- 1 ,2- dihydroquinoline Following the procedure of Example 35, l-E-(3-(4-bromophenyl)-l-oxo-2-propenyl)-2- cyano-1, 2-dihydroquinoline is used as the Reissert compound. The product, l-E-(3-(4- bromophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,?-dihydroquinoline, has a m.p. 180- 181°C. Example 36b l-E-[3-(4-bromophenyl)-l-oxo-2-propenyI]-N-(acetyloxy)-2- quinolinecarboximidamide The purified product of Example 36(a) is dissolved in 0.75 ml mediylene chloride. Pyridine (21 μl) is added and die reaction is cooled to 0°C. Acetic anhydride (25 μl) is added and die reaction stirred 15 min. at 0°C, and then brought to ambient temperature. After 1 h., the reaction is diluted with mediylene chloride, poured into saturated aqueous sodium bicarbonate, dried over sodium sulfate, and concentrated in vacuo. The residue is triturated widi 95% aqueous edianol and die solids collected to yield l-E-[3-(4-bromophenyl)-l- xo-2- propenyl]-N-(acetyloxy)-2-quinolinecarboximidamide (m.p. 151-153°C). Example 37a l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyI)-2-carboximidamide-l,2-dihydro- quinoline Following the procedure of Example 35, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyI)-2- cyano-l,2-dihydroquinoline is used as die Reissert compound. The product, l-E-(3-(4- chlorophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydroquinoline, has a m.p. 174- 175°C. Example 37b l-E-(3-(4-chIorophenyl)- 1 -oxo-2-propenyl)-2-carboximidamide-l ,2-dihydro- quinoline, hydrochloride The product of Example 37a, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2- carboximidamide-1, 2-dihydroquinoline, is dissolved in methanol and chlorotrimethyl silane is added. The addition of diethyl ether causes the desired salt to crystallize. The crystals are collected to afford l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydro- quinoline, hydrochloride (m.p. 15H-16CPC). Example 37c 1 -E-(3-(4-chlorophenyl)- 1 -oxo-2-propenyl)-2-carboximidamide- 1 ,2-dihydro¬ quinoline, mediane sulfonate The product of Example 37a, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2- carboximidamide-1, 2-dihydroquinoline, is dissolved in methanol and methane sulfonic acid is added. The volatiles are removed in vacuo and the residue recrystallized from diethyl ether/chloroform. The crystals are collected and dried to yield l-E-(3-(4-chlorophenyl)-l-oxo- 2-propenyl)-2-carboximidamide-l, 2-dihydroquinoline, mediane sulfonate (m.p. 139-140PQ. Example 37d l-E-[3-(4-chlorophenyl)-l-oxo-2-propenyl]-N-(acetyloxy)-2-quinoline- carboximidamide Following the procedure of Example 36(b) and making non-critical variations, but starting with the product of Example 37(a), l-E-3-(4-chlorophenyl)-l-oxo-2-propenyl)-2- carboximidamide-1, 2-dihydroquinoline, d e tide compound is obtained. l-E-[3-(4-chlorophenyl)- 1 -oxo-2-propenyl]-N-(acetyloxy)-2-quinolinecarboximidamide (m.p . 132-133°C) . Example 37e l-E-[3-(4-chlorophenyl)-l-oxo-2-propenyl]-N-methoxycarbonyloxy-2- quinolinecarboximidamide Following the general procedure as described for Examples 36(b) and making non-critical variations, but starting with the product of Example 37(a), l-E-(3-(4-chlorophenyl)-l-oxo-2- propenyl)-2-carboximidamide-l, 2-dihydroquinoline, and using methylchloroformate, the title compound is obtained, l-E-[3-(4-chlorophenyl)-l-oxo-2-propenyl]-N-methoxycarbonyloxy-2- quinolinecarboximidamide (m.p. 173-174°C). Example 38 l-E-(3-(4-hydroxyphenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2- dihydroquinoline Sodium carbonate (0.31 g) is dissolved in 2 ml of ethanol and 2 ml of water. Hydroxylamine hydrochloride (0.202 g) is added and die reaction is diluted with 40 ml of absolute ethanol . 1 -E-(3-(4-acetoxyphenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline (Example 14, 0.80 g) is added and die reaαion heated to reflux for 1.5 hours. After cooling, it is poured into 400 ml of ice water, and extracted widi chloroform (3 x 200 ml.) After concentration in vacuo, the residue is triturated widi 3 ml of methanol. The solids formed are collected to afford 199 mg of die tide compound (l-E-(3-(4-hydroxyphenyl)-l-oxo-2-propenyl)- 2-carboximidamide-l, 2-dihydroquinoline, m.p. 164-166°C). Example 39 l-(4-chlorobenzoyl)-8-fluoro-2-carboximidamide-l,2-dihydroquinoline Following the general procedure according to Example 38 and making non-critical variations, but using l-(4-chlorobenzoyl)-2-cyano-8-fluoro-l, 2-dihydroquinoline (Example 21) die tide compound is obtained (l-(4-chlorobenzoyl)-8-fluoro-2-carboxamidamide-l,2- dihydroquinoline, m.p. 186-187°C). Example 40 l-(4-chlorobenzoyl)-6,7-difluoro-2-carboximidamide-l,2-dihydro-quinoline Following Example 38 and using l-(4-chlorobenzoyl)-6,7-difluoro-2-cyano-l,2- dihydroquinoline (Example 24) the tide compound is obtained (l-(4-chlorobenzoyl)-6,7- difluoro-2-carboximidamide-l, 2-dihydroquinoline, m.p. 128-129°C). Example 41 l-(4-chlorobenzoyl)-6-fluoro-2-carboximidamide-l ,2-dihydroquinoline Following the general procedure of Example 38 and making non-critical variations, but using l-(4-chlorophenyl)-2-cyano-6-fluoro-l, 2-dihydroquinoline (Example 19), die tide compound is obtained (l-(4-chlorobenzoyl)-6-fluoro-2-carboximidamide-l, 2-dihydroquinoline, m.p. l62-163°C). Example 42a 1 -E-(3-(4-cyanophenyl)- 1 -oxo-2-propenyl)-2-carboximidamide- 1 ,2- dihydroquinoline Following the general procedure of Example 35 and making non-critical variations, but starting widi 1 -E-(3-(4-cyanophenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline (Example 11 , 0.20 g), the tide compound is obtained (l-E-(3-(4-cyanophenyl)-l- xo-2-propenyl)-2- carboximidamide-1, 2-dihydroquinoline, 0.1 lg, m.p. 205-206°C). Example 42b l-E-(3-(4-cyanophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2- dihydroquinoline hydrochloride The product of Example 42a (1.0 g) is suspended in 10 ml of methanol and concentrated hydrochloric acid (0.29 ml) is added. The solution is diluted widi etiier until crystals formed and tiien it is cooled to 5°C. The crystals are collected and dried to afford 0.68 g of die hydrochloride salt (l-E-(3-(4-cyanophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l ,2-dihydro- quinoline hydrochloride, m.p. 157-158°C). Biological Activity The utility of the compounds of die invention is demonstrated by d e ability of the compounds used to practice the method claimed in mis invention to inhibit viral reverse transcriptase, an enzyme essential for human immunodeficiency virus replication. This enzyme has characteristics which differentiate it from other known cellular polymerases and it is a unique enzyme which is not found in uninfected cells. Viral reverse transcriptase is found in extracts from bacterial clones prepared according to die procedure described by Larder, B., Purifoy D., Powell, K. and Darby, G., "AIDS Virus Reverse Transcriptase Defined by High Level Expression in Escherichia coli.", EMBO J. 6:3133-3137 (1987). Inhibition of this enzyme is determined in a cell free assay which measures the level of radioactive precursors incorporated into DNA. Extracts prepared according to the procedure of Kleid, D. G., et al., Science, 1125-1129 (1981) are incubated in a mixture of inhibitor, 20 mM ditiiiotiireitol, 60 mM sodium chloride, 0.05% NP-40, 10 mM magnesium chloride, 50 mM Tris pH 8.3, 10 μM [ 35 S]-Iabeled deoxynucleoside-5'-triphosphate, 10 μg/ml RNA template (poly rC or poly rG) and 5 μg/ml DNA primer (oligo dG or oligo dT) for 15 minutes at 37 °C. Incorporation of radio labeled precursor is determined by spotting aliquots of the reaction mixture on DE 81 paper, washing the papers to remove unicorporated precursor, drying, and determining counts. The results of various assays are combined and reported as % inhibition of reverse transcriptase activity at a 100 μM dose in Table I. The utility of this invention is further demonstrated by the ability of various compounds used to practice the method(s) claimed in this invention to inhibit HIV-induced syncytia formation in a tissue culture assay using MT-2 cells infected widi HIV-1. This test is described by Nara et al., "Quantitative infectivity assay for HIV-1 and -2", Nature 332: 469-470, 1988, as well as by Mariano Busso, et al., "Nucleotide Dinners Suppress HIV Expression in vitro' in AIDS RESEARCH AND HUMAN RETROVIRUSES, vol. 4, No. 6, pages 449-455 (1988), Mary Ann Liebent, Inc., Publishers. The results (IC 50 means the concentration, in μM of drug, required to inhibit syncytia formation to the extent of 50%) of various assays are combined and reported in Table I. In comparison, the known commercial compound, AZT, exhibited similar anti-HIV potency in this assay with 100 percent and 50 percent reductions in syncytia formation at concentrations of approximately 1 μM and 0.2 μM, respectively (data not shown). The utility of the compounds of the invention to practice the method claimed in this inven¬ tion is further demonstrated by die activity of this compound in die inhibition of HIV infection in primary peripheral blood lymphocytes (primary PBL assay). The primary PBL assay offers die following advantages: (a) The assays are performed with primary human lymphocytes. Thereby, undesired testing of transformed cell lines is avoided in which host cell and virus may have undergone processes of mutual adaptation. Performance of cell culture in serum containing media closely mimics the in vivo situation, (b) The primary PBL assay distinguishes between true antiviral effect which is due to the drug and cytostatic/cytotoxic reactions, (c) Viral replication is precisely followed by kinetic measurement of viral nucleic acids and proteins, (d) Nucleic acids (total HIV -RNA intra- and extracellular) and protein (secreted p24) are measured in parallel which permits one to differentiate between the compound's effect on virus replication and on die expression of viral proteins. This leads to additional information regarding die efficacy of the test compound, (e) Tolerance of the cell culture against low amounts of organic solvents also permits the investigation of hydrophobic substances, (f) The dose of die drug causing half maximal suppression of virus replication is determined, (g) The screening system is standardized and automated to a high degree. The primary PBL assay uses the following procedure: Effects of the compounds of die invention on cell proliferation are determined by lymphocyte proliferation assays. Starting with a 100 micromolar solution, the compound is serially diluted 10 fold. One tenth of the concentration of a compound causing half maximal inhibition of cellular proliferation is employed for all subsequent testing. Peripheral human lymphocytes are isolated by density gradient centrifugation. After stimulation by mitogen the cells are infected with a standardized preparation of HIV. Subsequendy, the infected cells are cultured in die presence of the drug for four days. Indivi¬ dual cultures are established to measure viral replication three and four days following infection. Untreated cells and AZT-treated cells are included as controls in parallel widi die drugs under investigation. The amount of viral core protein p24 synthesized and released by die infected cells is determined in the supernatant by die capture-ELISA technique on days three and four. By comparing with a standard preparation, the amount of protein produced by die virus infected cells is quantified. The total amount of viral RNA synthesized by die i ifected lymphocytes is determined by a special nucleic acid hybridization technique on days three and four of culture. By including a standard preparation of HIV-RNA the amount of synthesized RNA is quantified. If a drug shows antiviral effects in die primary assay, all steps of the primary assay are repeated. In addition, viability of HIV-infected cells is determined in parallel with assays for viral p24 and RNA. In order to evaluate die half maximal antiviral effect of the drug, a concentration dependency of die drug action is measured. The compounds of die invention are assayed according to this procedure. The anti-HIV activity, as measured by the inhibition of the release of core p24 protein in HIV infected human lymphocytes, is used to calculate antiviral ED50 (the concentration required to give a 50% reduction in p24 synthesis). Results are shown in Table I. FORMULAS 15 SUBSTITUTE SHEET CHART A W 10 CHART B 10 CHART C 20 TABLE I BIOASSAY RESULTS 1 TABLE 1 BIOASSAY RESULTS 1 (Continued) 1 - Assays are explained in specification. 2 - Known compound. 3 - Known compound: l-(4-toluoyl)-2-cyano-l, 2-dihydroquinoline.

Claims: wherein R 2 is -CN, -N 3 , -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C j -C 4 alkyl, -Ac, -C(O)OCH 3 , -C(O)OC 2 H 5 , -phenyl, -PO 2 -0 " cation + , -CO-CH(AA)NH 2 , -CO-C 6 H 6 -NR n R 12 , and -CO-C 6 H 6 -CH 2 -NR π R 12 ; AA is -CH 3 , -CH(CH 3 )2, -CH 2 CH(CH 3 )2,-CH 2 OH, -CH(OH)CH 3 , -CH 2 CO 2 H, Rn and R 12 may be the same or different and are hydrogen and C j -C alkyl; R u and R 12 taken together are morpholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N- (C!-C 4 alky piperazinyl; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen, -C 4 alkyl, -(CH^CN, and -(CH 2 )bR 13 ; R 13 is -N(CH 3 )2, -OH, -OPO 3 H, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 C(CH2) 2 CO 2 H, -OR 14 , and -NR 14 ; R 1 is a N-terminal amino acid; a is zero to six; b is one to five; A is CH, CH 2 , and CHN(CH 3 ) 2 ; X is CH, CH 2 , and C-R 4 ; R 4 is -CH 3 , -OCH 3 , and -OAc; R 5 , R 6 , R 7 , R 8 may be the same or different and are hydrogen and fluorine; W is oxygen and sulfur; Y j is -Cl, -F, -Br, -CH 3 , -CF 3 , -(CH 2 ) C R 17 , -CHO, -CO 2 CH 3 , -OH, -OCH 3> -OAc, -CN, - O j , -SH, and -SCH 3 ; c is zero to four; R 17 is -CH 2 N(CH 3 )2, -OH, -OPO 3 H, -CH 2 N(C2H 5 )2, -O-sugar, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 CCH 2 CH 2 CO2H, -CH 2 N=CHN(CH 3 )2, -OR lg , and -NR 18 ; R lg is a N-terminal amino acid; Y 2 is hydrogen; Y j and Y 2 taken together are -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO2CH 3 , -OH, -CN, and -OAc; provided, however, when A and X are each CH, and R 5 , R , R 7 , and Rg are each hydrogen, and R 2 is -CN, Y j is not -Cl, -F, or -CH 3 and R 19 is not hydrogen, when R 2 is -C(=NOH)N(R 10 )H and R 10 is hydrogen, R 19 is not hydrogen, when Yi is -OCH 3 , at least one of R 5 , Rg, R 7 or R 8 is fluorine, when Y } is -CF 3 , the connection between positions 3 and 4 is a double bond, or when Y j is -CF 3 and X is CH 2 and A is CHN(CH 3 ) 2 , the connection between 3 and 4 is a single bond, when R 4 is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Y t is -Cl, -F, -Br, -CF 3 , -CN, or -NO2, and when R 5 is fluorine, Rg, R 7 and R g are each hydrogen, or die pharmaceutically acceptable salts thereof. 2. A compound according to claim 1 wherein R 2 is -CN; R 3 is hydrogen; A is CH; X is CH and C-R 4 ; R 4 is -CH 3 ; R5, R 6 , R 7 , and Rg are each hydrogen; W is oxygen; Y! is -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OAc, -CN, -NO j , -SH, and -SCH 3 ; Y l and Y 2 taken together are -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO2CH 3 , -OH, -CN, and -OAc; provided, however, when A and X are each CH, and R 5 , Rg, R 7 , and Rg are each hydrogen, and R 2 is -CN, Y j is not -Cl, -F, or -CH 3 and R J9 is not hydrogen, and when R 4 is -CH 3 , Y { is -Cl, -F, -Br, -NO 2 , -CN, or -CF 3 . 3. A compound according to claim 2 selected from the group consisting of 1 -(4-bromobenzoyl)-2-cyano- 1 ,2-dihydroquinoline, l-(4-trifluoromedιylbenzoyl)-2-cyano-l,2-dihydroquinoline, 1 -(4-carbomethoxybenzoyI)-2-cyano- 1 ,2-dihydroquinoline, l-(4-chIorobenzoyl)-2-cyano-4-methyl-l ,2-dihydroquinoline, and 1 -(4-cyanobenzoyl)-2-cyano- 1 ,2-dihydroquinol ine. 4. A compound according to claim 1 wherein R 2 is -CN; R 3 is hydrogen; A is CH; X is CH or C-R 4 ; R 4 is -CH 3 ; R 5 , Rg, R 7 , and R g may be the same or different and are hydrogen and fluorine; W is oxygen; Y j is -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OCH 3 , -OAc, -CN, -NO j , -SH, and -SCH 3 ; Y 2 is hydrogen; Y j and Y 2 taken together are -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, that one of R 5 , Rg, R 7 , and Rg are fluorine, when R 4 is -CH 3 , Y χ is -Cl, -F, -Br, -CF 3 , -CN, or -NC^, and when R 5 is fluorine, Rg, R 7 , and Rg are each hydrogen. 5. A compound according to claim 4 selected from the group consisting of l-(4-chlorobenzoyl)-2-cy.ano-5-fluoro-l,2-dihydroquinoline, l-(4-chlorobenzoyI)-2-cyano-7-fluoro-l ,2-dihydroquinoline, l-(4-chlorobenzoyl)-2-cyano-6,7-difluoro-l,2-dihydroquinoline, l-(4-chlorobenzoyl)-2-cyano-6-fluoro-I,2-dihydroquinoIine, l-(4-methoxybenzoyl)-2-cyano-6,7-difluoro-l,2-dihydroquinoline, l-(4-chIorobenzoyl)-2-cyano-8-fluoro-l,2-dihydroquinoIine, l-(4-chlorobenzoyl)-6,8-difiuoro-2-cyano-l,2-dihydroquinoline, l-(4-chlorobenzoyl)-7,8-difluoro-2-cyano-l ,2-dihydroquinoline, and l-(4-chlorobenzoyl)-2-cyano-6,7,8-trifluoro-l,2-dihydroquinoline. 6. A compound according to claim 1 wherein R 2 is -CN; R 3 is hydrogen; A is CH 2 and CHN(CH 3 ) 2 ; X is CH 2 ; R 5 , Rg, R 7 , and Rg may be die same or different and are hydrogen and fluorine; W is oxygen; Y j is -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OCH 3> -OAc, -CN, -NO j , -SH, and -SCH 3 ; Y { and Y 2 taken together are -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, when Y j is -OCH 3 , at least one of R 5 , Rg, R 7 or Rg is fluorine, when R 5 is fluorine, Rg, R 7 , and Rg are each hydrogen, and when Y x is -CF 3 , A is CHN(CH 3 ) 2 . 7. A compound according to claim 6 selected from the group consisting of 1 -(4-chlorobenzoyl)-2-cyano- 1 ,2,3 ,4-tetrahydroquinoline, and l-(4-trifluorobenzoyl)-2-cyano-3-dimethylamino-l ,2,3,4-tetrahydroquinoline. 8. A compound according to claim 1 wherein R 2 is the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; RJO is hydrogen; R 1 is a N-terminal amino acid; R 3 is hydrogen; A is CH; X is CH; R 5 , Rg, R 7 , Rg may be the same or different and are hydrogen and fluorine; W is oxygen; Y γ is -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OCH 3j -OAc, -CN, -NO 2 , -SH, and -SCH 3 ; Y 2 is hydrogen; Y j and Y 2 taken together are -CH = CR 19 -CH = CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, when R 2 is -C(=NOH)N(R 10 )H and R 10 is hydrogen, R 19 is not hydrogen, when Y j is -OCH 3 , at least one of R5, Rg, R 7 or Rg is fluorine, and when R 5 is fluorine, Rg, R 7 , and R 8 are each hydrogen. 9. A compound according to claim 8 selected from the group consisting of l-(4-chIorobenzoyI)-2-carboximidamide-l,2-dihydroquinoIine, l-(4-chlorobenzoyl)-2-carboximidamide-8-fluoro-l,2-dihydroquinoline, l-(4-chlorobenzoyl)-2-carboximidamide-6,7-difluoro-l,2-dihydroquinoline, and l-(4-chIorobenzoyl)-6-fluoro-2-carboximidamide-l,2-dihydroquinoline. 10. A compound according to formula π wherein R 2 is -CN, -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C x -C 4 alkyl, -Ac, -C(O) CH 3 , -C(O)OC 2 H 5 , and -phenyl; A is CH and CH 2 ; X is NH; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen; R 5 , Rg, R 7 , Rg may be die same or different and are hydrogen and fluorine; W is oxygen; Y j is -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OCH 3 -OAc, -CN, -NO 2 , -SH, and -SCH 3 ; Y j and Y 2 taken together are -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, and -OAc; provided, however, when R 2 is -C(=NOH)N(R 10 )H and RJ Q is hydrogen, R 19 is not hydrogen; when Y j is -OCH 3 , at least one of R 5 , Rg, R 7 or R g is fluorine, when R 5 is fluorine, Rg, R 7 and Rg are each hydrogen; or the pharmacuetically acceptable salts thereof. 11. A compound according to claim 10 which is l-(4-chlorobenzoyl)-2-cyano-l,4- dihydroquinoxaline. 12. A compound according to formula I wherein R 2 is -CN, -N 3 , -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C^ alkyl, -Ac, -C(O)OCH 3 , - OJOC^H j , -phenyl, -PO 2 -O " cation + , -CO-CH(AA)NH 2 , -CO-C 6 H 6 -NR π R 12 , and -CO-C 6 H 6 -CH 2 -NR n R 12 ; AA is -CH 3 , -CH(CH 3 ) 2 , -CH 2 CH(CH 3 )2,-CH 2 OH, -CH(OH)CH 3 , -CH 2 CO 2 H, -CH 2 CH 2 CO 2 H, -(CH2) 4 NH 2 , and - CH^-NH j ; R j l and R 12 may be the same or different and are hydrogen and C j -C 4 alkyl; R j ! and R 12 taken together are moφholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N- (C j -C 4 alky piperazinyl; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen, C!-C 4 alkyl, -(CH^CN, and -(CH 2 )bR 13 ; R 13 is -N(CH 3 )2, -OH, -OPO 3 H, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 C(CH2) 2 CO 2 H, -OR 14 , and -NR 14 ; R 14 is a N-terminal amino acid; a is zero to six; b is one to five; ^0- A is CH, CH 2 , and CHN(CH 3 ) 2 ; X is CH, CH 2 , and C-R 4 ; R 4 is -CH 3 , -OCH 3 , and -OAc; R 5 , R 6 , R 7 , and Rg may be the same or different and are hydrogen and fluorine; W is oxygen and sulfur; Z is a linker selected from die group consisting of -(CO)-, -CH=CH-CH=CH- (all E), -CR 15 =CR 16 - (E or Z), or -CH=C=CH-; R j 5 and R 16 may be the same or different and are hydrogen and fluorine; Y χ is hydrogen, -Cl, -F, -Br, -CH 3 , -CF 3 , -(CH 2 ) C R 17 , -CHO, -CO 2 CH 3 , -OH, -OCH 3> -OAc, -CN, -NO 2 , -SH, and -SCH 3 ; c is zero to five; R 17 is -CH 2 N(CH 3 )2, -OH, -OPO 3 H, -CH 2 N(C 2 H 5 ) 2 , -O-sugar, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 CCH 2 CH 2 CO 2 H, -CH 2 N=CHN(CH 3 )2, -OR 18 , and -NR 18 ; R 18 is a N-terminal amino acid; Y 2 is hydrogen, -Cl, -F, -OCH 3 , and -CF 3 ; Y j and Y 2 taken together are -OCH 2 O-, -OC(CH 3 ) 2 O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S, or -SCH 2 O-; provided, however, when Z is -CR 15 =CR 16 - (E), and Y 2 , R 15 , and R 16 are each hydrogen, Y± is not hydrogen, when R 4 is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Y! is -Cl, -F, -Br, -CF 3 , -CN, or -NC^, and when R 5 is fluorine, Rg, R 7 and R 8 are each hydrogen, or die pharmaceutically acceptable salts thereof. 13. A compound according to claim 12 wherein R 2 is -CN and -N 3 . R 3 is hydrogen; A is CH; X is -CH and CH 2 ; R 5 , Rg, R 7 , and R 8 may be die same or different and are hydrogen and fluorine; W is oxygen; Z is a linker selected from the group consisting of -CH=CH-CH=CH- (all E) and -CR 15 =CR 16 - (E or Z); R j 5 and R 16 may be the same or different and are hydrogen and fluorine; Y χ is hydrogen, -Cl, -F. -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, - CH 3 -OAc, -CN, -NO2, -SH, and -SCH 3 ; Y 2 is hydrogen, -Cl, -F, -OCH 3 , and -CF 3 ; Y! and Y 2 taken together are - CH 2 O-, - C(CH 3 ) 2 O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S, or -SCH 2 O-; provided, however, when Z is -CR 15 =CR j g- (E), and Y 2 , R 15 , .and R j g are each hydrogen, Y j is not hydrogen, and when R 5 is fluorine, Rg, R 7 and R 8 are each hydrogen. 14. A compound according to claim 13 selected from the group consisting of 1 -E-(3-(4-trifluoromethylphenyl)- 1 -oxo-2-propenyI)-2-cyano- 1 ,2- dihydroquinoline, 1 -E-(3-(4-chlorophenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinol ine, 1 -E-(3-(4-fluorophenyl)-l -oxo-2-propenyl)-2-cyano-l ,2-dihydroquinoline, l-E-(3-(3,4-dichlorophenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, 1 -E-(2-fluoro- 1 -oxo-3-phenyl-2-propenyl)-2-cyano- 1 ,2-dihydroquinol ine, 1 -E-(3-(4-cyanophenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-cyano-6,7-difluoro-l,2-dihydroquinoline, l-E-(3-(4-acetoxyphenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, 1 -E-(3-(4-methoxyphenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline, 1 -Z-( 1 -oxo-3-phenyl-2-propenyI)-2-cyano- 1 ,2-dihydroquinoline, 1 -E-(3-(4-bromophenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline, l-E-(3-(4-carbomethoxybenzoyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, 1 -E-(3-(4-methylphenyl)- 1 -oxo-2-trans-propenyl)-2-cyano- 1 ,2-dihydroquinoline, l-E-(3-(3,4-methylenedioxyphenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, 1 -E-(3-(4-fluorophenyl)- 1 -oxo-2-propenyl)-2-cyano-6,7-difluoro- 1 ,2-dihydroquinoline, and 1 -E,E-(1 -oxo-2,4-pentadienyl-5-phenyl)-2-cyano-l ,2-dihydroquinoline. 15. A compound according to claim 14 which is l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2- cyano-1 ,2-dihydroquinoline. 16. A compound according to claim 12 wherein R 2 is the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, -Ac, and -C(O)OCH 3 ; R 3 is hydrogen; A is CH and CH 2 ; A2- X is CH and CH 2 ; R5, Rg, R 7 , and R 8 may be the same or different and are hydrogen and fluorine; W is oxygen; Z is -CR 15 =CR 16 - (E or Z); R j5 and R 16 may be the same or different and are hydrogen and fluorine; Y j is hydrogen, -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OAc, -CN, -NO2, -SH, and -SCH 3 ; Y 2 is hydrogen, -Cl, -F, -OCH 3 , and -CF 3 ; Y! and Y 2 taken together are -OCH 2 O-, -OC(CH 3 ) 2 O-, -OCH 2 NH-, -NHCH 2 0-, -OCH 2 S, or -SCH 2 O-; provided, however, when Y 2 , R 15 , and R |6 are each hydrogen, Y l is not hydrogen, and when R5 is fluorine, Rg, R 7 and Rg are each hydrogen. 17. A compound according to claim 16 selected from the group consisting of l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydroquinoline, l-E-(3-(4-chIorophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydroquinoline monohydrochloride, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydroquinoIine monomethane sulfonate, l-E-(3-(4-bromophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydroquinoline, l-E-(3-( iydroxyphenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydroquinoline, l-E-[3-(4-bromophenyl)-l-oxo-2-propenyl]-N-(acetyloxy)-2-quinolinecarboximidamide, 1 -E-[3-(4-chlorophenyI)- 1 -oxo-2-propenyl]-N-methoxycarbonyIoxy-2-quinolinecarb- oximidamide, l-E-[3-(4-chlorophenyl)-l-oxo-2-propenyl]-N-(acetyloxy)-2-quinolinecarboximidamide, 1 -E-(3-(4-cyanophenyl)- 1 -oxo-2-propenyl)-2-carboximidamide-l ,2-dihydroquinoline, and l-E-(3-(4-cyanophenyl)-l-oxo-2-propenyl)-2-carboximidamide-l,2-dihydroquinoline monohydrochloride. 18. Use of a compound of formula I wherein R 2 is -CN, -N 3 , -SCN, and the E or Z isomers of -C(=NOR 10 )NH 2 , -C(=NR 10 )H, -C(=NNR 10 )NH 2 , -C(=NR 10 )NH 2 , -C(=NOR 10 )H, and -C(=NOH)N(R 10 )H; R 10 is hydrogen, C^ alkyl, -Ac, -CO 2 CH 3 , -CO 2 C 2 H 5 , -phenyl, -PO 2 -O" cation "1" , -CO-CH(AA)NH 2 , -CO-C 6 Hg-NR n R 12 , and -CO-CgHg-O^-NRnR^; AA is -CH 3 , -CH(CH 3 ) 2 , -CH 2 CH(CH 3 ) 2 ,-CH 2 OH, -CH(OH)CH 3 , -C^CC^H, -CH 2 CH 2 CO2H, -(CH2) 4 NH 2 , and -(CH 2 ) 3 -NH 2 ; R j ! and R j2 may be the same or different and are hydrogen and C j -C 4 alkyl; R j j and R 12 taken together are moφholinyl, piperazinyl, pyrrolidinyl, piperadinyl, and N- (C j -C 4 alky piperazinyl; R 3 , present when the connection between positions 2 and 3 is a single bond, is hydrogen, -C 4 alkyl, -(CH^CN, and -(CH^R^; R 13 is -N(CH 3 ) 2 , -OH, -OPO 3 H, -OCH 2 CH(-OH)CH 2 OH, -OCH 2 CO 2 H, -O^CH^CO^, -OR 14 , and -NR 14 ; R 14 is a N-terminal amino acid; a is zero to six; b is one to five; A is CH, CH 2 , N, and CHN(CH 3 ) 2 ; X is CH, CH 2 , NH, O, and C-R 4 ; R 4 is -CH 3 -OCH 3 , and -OAc; R 5 , Rg, R 7 , and R 8 may be the same or different and are hydrogen and fluorine; W is oxygen and sulfur; Z is a direct bond or a linker selected from the group consisting of -(CO)-, -CH=CH-CH=CH- (all E), -CR 15 =CR 16 - (E or Z), and -CH=C=CH-; R j 5 and R 16 may be the same or different and are hydrogen and fluorine; Y j is hydrogen, -Cl, -F, -Br, -CH 3 , -CF 3 , -(CH^R^ -CHO, -CO 2 CH 3 , -OH, -OCH 3> -OAc, -CN, -NU2, -SH, and -SCH 3 ; c is zero to five; R 17 is -CH 2 N(CH 3 )2, -OH, -OPO 3 H, -CH 2 N(C 2 H 5 )2, -O-sugar, -OCH 2 CH(OH)CH 2 OH, -OCH 2 CO 2 H, -O 2 CCH 2 CH 2 CO 2 H, -OR 18 , or - Rig; R 18 is an N-terminal amino acid; Y 2 is hydrogen, -Cl, -F, -OCH 3 , and -CF 3 ; Y j and Y 2 taken together can form -OCH 2 O-, -OC(CH 3 ) 2 O-, -OCH 2 NH-, -NHCH 2 O-, -OCH2S-, -SCH 2 O-, and -CH=CR 19 -CH=CH-; R 19 is hydrogen, -Cl, -Br, -NO 2 , -CF 3 , -CO 2 CH 3 , -OH, -CN, -and -OAc; provided, however, when Z is a direct bond and R 2 is -C(=NOH)N(R 10 )H and R 10 is hydrogen, R 19 is not hydrogen, when Z is a direct bond, Y j is not hydrogen, when Y j is -OCH 3 and Z is a direct bond, at least one of R5, Rg, R 7 or Rg is fluorine, when Y j is -CF 3 and Z is direct bond, die connection between positions 3 and 4 is a double bond, when Z is a direct bond, X is not O, when Z is a direct bond, R 2 is not -N 3 , when Z is a direct bond, Y 2 is hydrogen or -F, when A is N, X is C-R 4 and R 4 is -OCH 3 or -OAc and the connection between position 3 and 4 is a double bond, when A is CHN(CH 3 ) 2 , X is CH 2 , when R 4 is -CH 3 , R 3 is hydrogen, when R 4 is -CH 3 , Y χ is -Cl, -F, -Br, -CF 3 , -CN, or -NC^, when R 5 is fluorine, Rg, R 7 and R 8 are each hydrogen, when Y j and Y 2 taken togedier are -CH=CR 19 -CH=CH-, Z is a direct bond, and when Y t and Y 2 taken together can form -OCH 2 O-, -O CH^ -, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S-, and -SCH 2 O-, Z is a linker, and/or die pharmaceutically acceptable salts, hydrates, and solvates thereof for the manufacture of a medicament for use in treating a human infected widi one or more than one strain of a human immunodeficiency virus (HIV). 19. The use according to claim 18 wherein R 2 is -CN and -N 3 . R 3 is hydrogen; A is CH; X is -CH and CH 2 ; R 5 , Rg, R 7 , and R 8 may be the same or different and are hydrogen and fluorine; W is oxygen; Z is a linker selected from the group consisting of -CH=CH-CH=CH- (all E) and -CR 15 =CR 16 - (E or Z); R 15 and R 16 may be the same or different and are hydrogen and fluorine; Yi is hydrogen, -Cl, -F, -Br, -CH 3 , -CF 3 , -CHO, -CO 2 CH 3 , -OH, -OCH 3( -OAc, -CN, -NO2, -SH, and -SCH 3 ; Y 2 is hydrogen, -Cl, -F, -OCH 3 , and -CF 3 ; Y j and Y 2 taken together are -OCH 2 O-, -OC(CH 3 ) 2 O-, -OCH 2 NH-, -NHCH 2 O-, -OCH 2 S, or -SCH 2 O-; provided, however, when Z is -CR^CR j g- (E), and Y 2 , R 15 , and R 16 are each hydrogen, Y j is not hydrogen, and when R5 is fluorine, Rg, R 7 and Rg are each hydrogen. 20. The use according to claim 19 wherein die compound is 1 -E-(3-(4-trifluoromethylphenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2- dihydroquinoline, 1 -E-(3-(4-chlorophenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline, l-E-(3-(4-fluorophenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, l-E-(3-(3,4-dichlorophenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, l-E-(2-fluoro-l-oxo-3-phenyl-2-propenyl)-2-cyano-l,2-dihydroquinoline, 1 -E-(3-(4-cyanophenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline, l-E-(3-(4-chlorophenyl)-l-oxo-2-propenyl)-2-cyano-6,7-difluoro-l,2-dihydroquinoline, 1 -E-(3-(4-acetoxyphenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinol ine, l-E-(3-(4-medιoxyphenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoIine, 1 -Z-( 1 -oxo-3-phenyl-2-propenyl)-2-cyano- 1 ,2-dihydroquinoline, 1 -E-(3-(4-bromophenyl)- 1 -oxo-2-propenyl)-2-cyano- 1 ,2-dihydroquinol ine, l-E-(3-(4-carbomethoxybenzoyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, 1 -E-(3-(4-methylphenyl)- 1 -oxo-2-trans-propenyl)-2-cyano- 1 ,2-dihydroquinoline, l-E-(3-(3,4-methylenedioxyphenyl)-l-oxo-2-propenyl)-2-cyano-l,2-dihydroquinoline, l-E-(3-(4-fluorophenyl)-l-oxo-2-propenyl)-2-cyano-6,7-difluoro-l,2-dihydroquinoline, and l-E,E-(l-oxo-2,4-pentadienyl-5-phenyl)-2-cyano-l,2-dihydroquinoline.

Inventors: ALTHAUS IRENE WILSON, ARISTOFF PAUL ADRIAN, BANNISTER BRIAN, BILES CAROLYN, MARTIN DAVID GLENN, REUSSER FRITZ, ROMERO DONNA LEE, SKULNICK HARVEY IRVING, SMITH HERMAN WALDEN, ALTHAUS, IRENE, WILSON, ARISTOFF, PAUL, ADRIAN, BANNISTER, BRIAN, BILES, CAROLYN, MARTIN, DAVID, GLENN, REUSSER, FRITZ, ROMERO, DONNA, LEE, SKULNICK, HARVEY, IRVING, SMITH, HERMAN, WALDEN
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1992
Main classification: C07D241
IPC codes: A61K31, A61P31, A61P37, C07D215, C07D241, C07D405