Abstract: Thrombin inhibitors represented by the formula ##STR1## as provided wherein A(C.dbd.O)-- is, inter alia, phenylglycyl, cyclohexylglycyl, cyclohexenylglycyl, thienylglycyl or naphthylglycyl, wherein the .alpha.-amino group is preferably substituted by alkyl e.g. methyl or an alkoxycarbonyl, cycloalkoxycarbonyl or arylkoxycarbonyl group e.g. t-butyloxycarbonyl. A(C.dbd.O)-- also represents an .alpha.-substituted acetyl group such as .alpha.-methoxyphenylacetyl; or a bicyclic group such as a tetrahydroisoquinolin-1- or 3-carbonyl group; a perhydroisoquinolin -1- or -3-carbonyl group; or a 1-amino or (substituted amino) cycloalkylcarbonyl group such as 1-aminocyclohexylcarbonyl. Also provided are a method for inhibiting the formation of blood clots in man and animals by administering a thrombin inhibitor of the above formula and pharmaceutical formulations useful in the method.

Abstract: A method is disclosed for the rapid synthesis of very large numbers of peptides which can be integrated with the screening of these peptides as heterogeneous mixtures to identify the specific peptides which demonstrate biological activity using a small number of coupling steps.

Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in whichR is hydrogen, methyl, ethyl, cyclopropylmethyl, or allyl;A is a residue of a D-amino acid selected from the goup consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp) Met, Cys(Me), Met(O), Cys(Me) (O), Ser, Ser(Me), Thr, and Hse;R.sub.1 is hydrogen, C.sub.1 -C.sub.3 primary alkyl, cyclopropylmethyl, allyl, ethylthiomethyl, 2-fluoroethyl, or propargyl; andX is hydrogen, fluoro, bromo, iodo, chloro, hydroxy, C.sub.1 -C.sub.3 alkyl, trifluoromethyl, or C.sub.1 -C.sub.2 alkoxy; are useful analgesic agents.

Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in whichR is hydrogen, methyl, ethyl, cyclopropylmethyl, or allyl;A is a residue of a D-amino acid selected from the group consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp), Met, Cys(Me), Met(O), Cys(Me)(O), Ser, Ser(Me), Thr, and Hse;R.sub.1 is hydrogen, C.sub.1 -C.sub.3 primary alkyl, cyclopropylmethyl, allyl, ethylthiomethyl, 2-fluoroethyl, or propargyl; andX is hydrogen, fluoro, bromo, iodo, chloro, hydroxy, C.sub.1 -C.sub.3 alkyl, trifluoromethyl, or C.sub.1 -C.sub.2 alkoxy; are useful analgesic agents.

Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in whichL and D define the chirality;R.sub.1 is hydrogen or C.sub.1 -C.sub.3 primary alkyl;R.sub.2 is C.sub.1 -C.sub.4 primary or secondary alkyl, allyl, cyclopropylmethyl, C.sub.1 -C.sub.2 hydroxyalkyl, or --(CH.sub.2).sub.m -U-CH.sub.3 in which U is --S-- or ##STR2## and m is 1 or 2; R.sub.3 is hydrogen, C.sub.1 -C.sub.4 primary or secondary alkyl, cyclopropylmethyl, or allyl;R.sub.4 is hydrogen, C.sub.1 -C.sub.5 primary or secondary alkyl, --(CH.sub.2).sub.n --X--(CH.sub.2).sub.p --CH.sub.3 in which X is --O--, --S--, ##STR3## n is 1 or 2, and p is 0 or 1, phenyl, or monosubstituted phenyl in which the substituent is halo, hydroxy, C.sub.1 -C.sub.3 alkoxy, nitro, C.sub.1 -C.sub.3 alkyl, or trifluoromethyl;R.sub.5 is hydrogen or C.sub.1 -C.sub.4 primary alkyl; andZ is --CH.sub.2 OR.sub.6, ##STR4## in which R.sub.6 is hydrogen or C.sub.1 -C.sub.3 alkyl and R.sub.7 is C.sub.1 -C.sub.

Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in whichR is hydrogen, methyl, ethyl, cyclopropylmethyl, or allyl;A is a residue of a D-amino acid selected from the group consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp), Met, Cys(Me), Met(O), Cys(Me) (O), Ser, Thr, and Hse;R.sub.1 is C.sub.1 -C.sub.3 primary alkyl, cyclopropylmethyl, allyl, ethylthiomethyl, 2-fluoroethyl, or propargyl;X is bromo, iodo, chloro, methyl, trifluoromethyl, or methoxy; andZ is --CH.sub.2 OR.sub.2, ##STR2## in which R.sub.2 is hydrogen, acetyl, or acetoxymethyl and R.sub.3 is C.sub.1 -C.sub.3 alkyl; are useful analgesic agents.

Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in whichR is hydrogen, methyl, or ethyl;A is the residue of a D-amino acid selected from the group consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp), Met, Cys(Me), Met(O), Cys(Me) (O), Ser, Thr, and Hse;R.sub.1 is hydrogen, C.sub.1 -C.sub.3 primary alkyl, cyclopropylmethyl, allyl, or propargyl;X is bromo, iodo, chloro, C.sub.1 -C.sub.3 alkyl, trifluoromethyl, or C.sub.1 -C.sub.2 alkoxy;B is the residue of a D- or L-amino acid lacking its carboxyl moiety and selected from the group consisting of Gly, Ala, Abu, Nva, Val, Nle, Leu, Ile, Pgl, Cys(Me), Cys(Me) (O), Cys(Me) (O.sub.2), Cys(Et), Cys(Et) (O), Cys(Et) (O.sub.2), Met, Met(O), Met(O.sub.2), Eth, Eth(O), Eth(O.sub.2), Ser(Me), Ser(Et), Hse(Me), and Hse(Et) as well as any of such residues substituted at the amino nitrogen by a C.sub.1 -C.sub.3 primary alkyl;Z is --CH.sub.2 OR.sub.2, ##STR2## in which R.sub.2 is hydrogen or C.sub.1 -C.

Abstract: Compounds of the formula[R-Tyr-A-Gly-(N-R.sub.1)Phe(p-Y)-X].sub.2 -(CH.sub.2).sub.nin whichR is hydrogen or methyl;A is the residue of a D-amino acid selected from the group consisting of Ala, Abu, Ser, Thr, and Met;R.sub.1 is hydrogen, C.sub.1 -C.sub.3 primary alkyl, cyclopropylmethyl, or allyl;Y is hydrogen or fluoro;n is an integer from 1 to 10; andX is --NH-- or a group of the formula ##STR1## in which R.sub.2 is hydrogen or C.sub.1 -C.sub.3 primary alkyl; R.sub.3 is phenyl, 2-methylthioethyl, or isobutyl; or R.sub.2 and R.sub.3 taken together are --CH.sub.2 --CH.sub.2 --CH.sub.2 --;subject to the limitation that, when R.sub.2 is other than hydrogen, R.sub.1 is hydrogen; are useful analgesic agents.

Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality;R.sub.1 is hydrogen or C.sub.1 -C.sub.3 primary alkyl;R.sub.2 is C.sub.1 -C.sub.4 primary or secondary alkyl, allyl, cyclopropylmethyl, C.sub.1 -C.sub.2 hydroxyalkyl, or --(CH.sub.2).sub.m --U--CH.sub.3 in which U is --S-- or >S--O and m is 1 or 2;R.sub.3 is hydrogen, C.sub.1 -C.sub.4 primary or secondary alkyl, cyclopropylmethyl, or allyl;R.sub.4 is hydrogen, C.sub.1 -C.sub.5 primary or secondary alkyl, --(CH.sub.2).sub.n --X--(CH.sub.2).sub.p --CH.sub.3 in which X is --O--, --S--, >S--O or ##STR2## n is 1 or 2, and p is 0 or 1, phenyl, or monosubstituted phenyl in which the substituent is halo, hydroxy, C.sub.1 -C.sub.3 alkoxy, nitro, C.sub.1 -C.sub.3 alkyl, or trifluoromethyl;R.sub.5 is hydrogen or C.sub.1 -C.sub.4 primary alkyl; andZ is --CH.sub.2 OR.sub.6, ##STR3## in which R.sub.6 is hydrogen or C.sub.1 -C.sub.3 alkyl and R.sub.7 is C.sub.1 -C.sub.

Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality;R.sub.1 is hydrogen or C.sub.1 -C.sub.3 primary alkyl;R.sub.2 is C.sub.1 -C.sub.4 primary or secondary alkyl, allyl, cyclopropylmethyl, C.sub.1 -C.sub.2 hydroxyalkyl, or --(CH.sub.2).sub.m --U--CH.sub.3 in which U is --S-- or >S--O and m is 1 or 2;R.sub.3 is hydrogen, C.sub.1 -C.sub.4 primary or secondary alkyl, cyclopropylmethyl, allyl or propargyl; andZ is --CH.sub.2 OR.sub.4, ##STR2## in which R.sub.4 is hydrogen, acetyl, or acetoxymethyl and R.sub.5 is C.sub.1 -C.sub.3 alkyl; are useful analgesic agents.

Abstract: Compound of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality;R.sub.1 is hydrogen or C.sub.1 --C.sub.3 primary alkyl;R.sub.2 is C.sub.1 --C.sub.4 primary or secondary alkyl, allyl, cyclopropylmethyl, C.sub.1 --C.sub.2 hydroxyalkyl, or --(CH.sub.2).sub.m --U--CH.sub.3 in which U is --S-- or >S--O and m is 1 or 2;R.sub.3 is hydrogen, C.sub.1 --C.sub.4 primary or secondary alkyl, cyclopropylmethyl, or allyl;X is hydrogen, halo, hydroxy, C.sub.1 --C.sub.3 alkoxy, nitro, C.sub.1 --C.sub.3 alkyl, or trifluoromethyl; andZ is --CH.sub.2 OR.sub.4, ##STR2## in which R.sub.4 is hydrogen or C.sub.1 --C.sub.3 alkyl and R.sub.5 is C.sub.1 --C.sub.3 alkyl; are useful analgesic agents.