Abstract: Phosphoramidates and phosphinic amides and related compounds are provided. Also provided are methods that use the compounds for modulating the activity of the endothelin family of peptides are provided. In particular, compounds having formula: ##STR1## in which A, B, R.sup.1 and R.sup.2 are as described are provided. Also provided are methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these compounds or prodrugs thereof. Methods for elucidating the physiological and pathophysiological roles of endothelin, as well as isolating endothelin receptors are also provided.

Abstract: The present invention provides compounds having structure (II), and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof.

Abstract: Methods, compositions, and compounds for modulating the activity of an endothelin peptide are provided. The methods use compositions that contain compounds that include those of the formula: ##STR1## where X is selected from groups that include O, S, and NH; Y is selected from O.sup.+ and N, and R.sup.1 and R.sup.2 are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.2 is not halide. R.sup.3, R.sup.4 and R.sup.5 are selected from among groups that include hydrogen, halide, alkoxy, alkyl, haloalkyl; and R.sup.7 is selected from groups that include (CH.sub.2).sub.r R.sup.18, in which r is 0 to 6 and R.sup.18 is selected from groups that include aryl, particularly pyrmidinyl and phenyl.

Abstract: A process of preparing an alkali metal salt of a hydrophobic sulfonamide is provided. The process includes the step of dissolving a free sulfonamide in an organic solvent in the presence of a saturated alkali metal salt solution and recovering the formed sulfonamide salt from the organic phase.

Abstract: The present invention provides conjugates of mitomycin C or derivatives thereof and oligonucleotides. A conjugate of the present invention corresponds to formula I, below: ##STR1## where R is H, CH.sub.3, or C(O)SCH.sub.3, R' is O or NH, m is an integer from 1 to 10 and Ogn is an oligonucleotide. Pharmaceutical compositions and methods of using such conjugates to inhibit gene product expression are also provided.

Abstract: Cyclic peptides and pharmaceutically acceptable salts and esters thereof are provided. The cyclic peptides and pharmaceutically acceptable salts and esters thereof mimic surface features of the C-terminus of endothelin and thereby can be used modulate or alter the activity of the endothelin family of peptides. More particularly, cyclic pentapeptides, cyclic hexapeptides, cyclic heptapeptides and pharmaceutically acceptable derivatives of the peptides that specifically inhibit the activity of endothelin are provided. Among the cyclic peptides are those that have the formula: cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -D-Trp): X.sup.1 is D-Tyr or D-Asp; X.sup.2 is Phe, Ala, Ac.sub.3 c or Pro; X.sup.3 is D-His, D-Ala, D-Val, Gly or .beta.-Ala; and X.sup.4 is His, Ala, .beta.-Ala, Aib, Gly, D-His-gly or Leu; cyclo(X.sup.1 -L-Phe-X.sup.3 -X.sup.4 -X.sup.5) in which X.sup.1 is D-Tyr, D-Asp or D-Glu, X.sup.3 is selected from among D-His, .beta.-Ala-D-His or gly-D-His; X.sup.4 is Ser, Gly or .beta.-Ala, and X.sup.

Abstract: A process of preparing mannosylated alcohols or phenols in high chemical yield and purity using tetra-O-pivaloylmannosylfluoride and a Lewis acid catalyst.

Abstract: This invention relates to compounds that inhibit the binding of E-selectin or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface having the general structure: ##STR1## This invention also relates to methods of inhibiting the binding of E-selectin or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface using said compounds and to pharmaceutically active compositions comprising compounds that inhibit the binding of E-selectin to sialyl-Lewis.sup.x and to methods of treatment of septic shock, ARDS, Crohn's disease, chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis, and reperfusion injuries that occurs following heart attacks, strokes and organ transplants and to the treatment of cancer.

Abstract: Thienyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: Thiophenyl-, furyl- and pyrrolyl-sulfonamides and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, isoxazolyl-thiophenyl-sulfonamides, isoxazolyl-furyl-sulfonamides and isoxazolyl-pyrrolyl-sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided.

Abstract: Sulfonamides and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit or increase the activity of endothelin are also provided. The sulfonamides have formula I: ##STR1## in which Ar.sup.1 is a 3- or 5-isoxazolyl and Ar.sup.2 is selected from among alkyl, including straight and branched chains, aromatic rings, fused aromatic rings and heterocyclic rings, including 5-membered heterocycles with one, two or more heteroatoms and fused ring analogs thereof and 6-membered rings with one, two or more heteroatoms and fused ring analogs thereof. Ar.sup.2 is preferably thiophenyl, furyl, pyrrolyl, naphthyl, and phenyl. Compounds in which Ar.sup.

Abstract: The present invention is directed to an isolated and purified peptide comprising the LDV domain of the CSI peptide sequence or single amino acid substitutent analog thereof. A preferred peptide has the amino acid residue sequences shown in SEQ ID NOs:8-14, 17-23, 25, 28, and 51. The present invention is further directed to a process of inhibiting the binding of .alpha..sub.4 .beta..sub.1 integrin to a protein such as VCAM-1 or fibronectin comprising exposing a cell that expresses .alpha..sub.4 .beta..sub.1 integrin to the protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition comprising a peptide of SEQ ID NO:8-102.

Abstract: This invention relates to compounds that inhibit the binding of E-selectin and/or P-selectin to sialyl-Lewis.sup.x or sialyl-Lewis.sup.a presented on a cell surface having the general structure ##STR1## wherein X is selected from the group consisting of --(CH.sub.2).sub.n CO.sub.2 H, --O(CH.sub.2).sub.m CO.sub.2 H, --(CH.sub.2).sub.n O(CH.sub.2).sub.m CO.sub.2 H, --CONH(CH.sub.2).sub.m CO.sub.2 H, --CH(OZ)(CO.sub.2 H), --CH(Z)(CO.sub.2 H), --(CH.sub.2).sub.n SO.sub.3 H, --(CH.sub.2).sub.n PO.sub.3 D.sub.1 D.sub.2, --NH(CH.sub.2).sub.m CO.sub.2 H, --CONH(CHR.sub.6)CO.sub.2 H, (1-H-tetrazolyl-5-alkyl-), and --OH;R.sub.1 and R.sub.2 are independently selected from the group consisting of hydrogen, alkyl, halogen, --OZ, --NO.sub.2, --NH.sub.2 and --NHZ;R.sub.3 is selected from the group consisting of hydrogen, halogen, alkyl, --OZ and --NHZ;R.sub.4 is selected from the group consisting of hydrogen, halogen, alkyl, hydroxyl, hydroxyl-O-sulfate and --OZ;R.sub.