Phosphorus containing compounds

Claim 1

A method of preparing compounds having the formula and pharmaceutically acceptable salts thereof wherein: R 1 and R 2 are independently selected from the group consisting of hydrogen, lower alkyl, halo substituted lower alkyl, and amino substituted lower alkyl; or n is zero or one; q is zero or an integer from 1 to 7; R 21 is hydrogen, lower alkyl, halo substituted lower alkyl, benzyl, or phenethyl; R 22 is hydrogen or lower alkyl; R 23 is hydrogen, lower alkyl, halo substituted lower alkyl, -(CH 2 ) r -NH 2 , -(CH 2 ) r -SH, -(CH 2 ) r -S-lower alkyl, or X is an imino or amino acid of the formula R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, azido, amino, a 1- or 2-naphthyl of the formula O-lower alkyl, a 1- or 2-naphthyloxy of the formula , -S-lower alkyl, or a 1- or 2-naphthylthio of the formula R 8 is keto, halogen, O-lower alkyl, a 1- or 2-naphthyloxy of the formula -S-lower alkyl, or a 1- or 2-naphthylthio of the formula R 9 is keto or R 10 is halogen or - Y-R 16 ; R 11 , R' 11 , R12 and R ' 12 are independently selected from hydrogen and lower alkyl or R' 11 , R 12 and R ' 12 are hydrogen and R 11 is R 13 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy or 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, hydroxy, phenyl, phenoxy, phenylthio, or phenylmethyl; R 14 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, or hydroxy; m is zero, one, two or three; p is one, two or three provided that p is more than one only if R 13 or R 14 is hydrogen, methyl, methoxy, chloro, or fluoro; R 15 is hydrogen or lower alkyl of 1 to 4 carbons; Y is oxygen or sulfur; R 16 is lower alkyl of 1 to 4 carbons, , or the R 16 groups join to complete an unsubstituted 5- or 6-membered ring or said ring in which one or more of the carbons has a lower alkyl of 1 to 4 carbons or a di(lower alkyl of 1 to 4 carbons) substituent; R 4 is hydrogen, lower alkyl, cycloalkyl, or R5 is hydrogen, lower alkyl, -(CH 2 ) r -NH 2 , -(CH 2 ) r -SH, -(CH 2 ) r -S-lower alkyl, or r is an integer from 1 to 4; R 3 and R 6 are independently selected from the group consisting of hydrogen, lower alkyl, benzyl, benzhvdrvl. and wherein R 17 is hydrogen, lower alkyl, or phenyl, and R 18 is hydrogen, lower alkyl, lower alkoxy, phenyl, or R 17 and R 18 taken together are -(CH 2 ) 2 -, -(CH 2 ) 3 -, - CH= C H, or R 19 is lower alkyl, benzyl, or phenethyl; and R 20 is hydrogen, lower alkyl, benzyl or phenethyl, which comprises, when A is of reacting the corresponding carboxylic acid of the compound represented by the formula: or its activated form with a compound represented by the formula: (X) Hx in the presence of a coupling agent to yield the compounds of formula I.

Claim 2

A method of preparing compounds having the formula and pharmaceutically acceptable salts thereof wherein: R 1 and R 2 are independently selected from the group consisting of hydrogen, lower alkyl, halo substituted lower alkyl, and amino substituted lower alkyl; or n is zero or one; q is zero or an integer from 1 to 7; R 21 is hydrogen, lower alkyl, halo substituted lower alkyl, benzyl, or phenethyl; R 22 is hydrogen or lower alkyl; R 23 is hydrogen, lower alkyl, halo substituted lower alkyl, -(CH 2 ) r -NH 2 , -(CH 2 ) r -SH, -(CH 2 ) r -S-lower alkyl, or X is an imino or amino acid of the formula R 7 is hydrogen, lower alkyl, halogen, keto, hydroxy, azido, amino, a 1- or 2-naphthyl of the formula O-lower alkyl, a 1- or 2-naphthyloxy of the formula , -S-lower alkyl, or a 1- or 2-naphthylthio of the formula R 8 is keto, halogen, O-lower alkyl, a 1- or 2-naphthyloxy of the formula -S-lower alkyl, or a 1- or 2-naphthylthio of the formula R 9 is keto or R 10 is halogen or - Y-R 16 ; R 11 , R' 11 , R12 and R ' 12 are independently selected from hydrogen and lower alkyl or R' 11 , R 12 and R ' 12 are hydrogen and R 11 is R 13 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy or 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, hydroxy, phenyl, phenoxy, phenylthio, or phenylmethyl; R 14 is hydrogen, lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, or hydroxy; m is zero, one, two or three; p is one, two or three provided that p is more than one only if R 13 or R 14 is hydrogen, methyl, methoxy, chloro, or fluoro; R 15 is hydrogen or lower alkyl of 1 to 4 carbons; Y is oxygen or sulfur; R 16 is lower alkyl of 1 to 4 carbons, , or the R 16 groups join to complete an unsubstituted 5- or 6-membered ring or said ring in which one or more of the carbons has a lower alkyl of 1 to 4 carbons or a di(lower alkyl of 1 to 4 carbons) substituent; R 4 is hydrogen, lower alkyl, cycloalkyl, or R5 is hydrogen, lower alkyl, -(CH 2 ) r -NH 2 , -(CH 2 ) r -SH, -(CH 2 ) r -S-lower alkyl, or r is an integer from 1 to 4; R 3 and R 6 are independently selected from the group consisting of hydrogen, lower alkyl, benzyl, benzhvdrvl. and wherein R 17 is hydrogen, lower alkyl, or phenyl, and R 18 is hydrogen, lower alkyl, lower alkoxy, phenyl, or R 17 and R 18 taken together are -(CH 2 ) 2 -, -(CH 2 ) 3 -, - CH= C H, or R 19 is lower alkyl, benzyl, or phenethyl; and R 20 is hydrogen, lower alkyl, benzyl or phenethyl, which comprises, when A is of reacting the corresponding carboxylic acid of the compound represented by the formula: or its activated form with a compound represented by the formula: (X) Hx in the presence of a coupling agent to yield the compounds of formula I.