Abstract: A compound of the formulae (I) or (II): wherein: Y is a moiety selected from NR or —(CH2)n; wherein R is hydrogen or (C1-C6) lower alkyl, and n is 1; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C1-C6) lower alkyl, halogen or (C1-C6) lower alkoxy; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, or (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 5-membered aromatic (unsaturat

Abstract: Novel sulfonamide compounds useful in the treatment of conditions related to the production of beta-amyloid are described, as are routes to their preparation. The sulfonamide compounds are of the following structure, wherein R1-R3 are defined herein. Also provided are pharmaceutical compositions containing these compounds and/or prodrugs of these compounds and a physiologically compatible carrier. These compounds are specifically useful for inhibiting beta amyloid production, and treating Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, mild cognitive impairment (MCI) and Down's syndrome.

Abstract: A compound of the formulae (I) or (II): wherein: Y is a moiety selected from NR or —(CH2)n; wherein R is hydrogen or (C1-C6) lower alkyl, and n is 1; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C1-C6) lower alkyl, halogen or (C1-C6) lower alkoxy; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, or (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 5-membered aromatic (unsaturated

Abstract: The present invention provides compounds of the general formulas: wherein Y is NR or —(CH2)n; R is H or alkyl; “Z” represents optionally substituted phenyl or a 6-membered aromatic ring having one nitrogen atom; “W” represents a optionally substituted phenyl or 5-membered aromatic ring having one nitrogen atom; “X” represents an optionally substituted 5-membered aromatic ring having one sulfur atom; as well as methods and pharmaceutical compositions utilizing these compounds for the inducing temporary delay of urination or treatment of disorders remedied by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, or bleeding and coagulation disorders.

Abstract: A compound of the formulae (I) or (II): wherein: Y is a moiety selected from NR or —(CH2)n; wherein R is hydrogen or (C1-C6) lower alkyl, and n is 1; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C1-C6) lower alkyl, halogen or (C1-C6) lower alkoxy; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C1-C6) lower alkyl, halogen, cyano, CF3, hydroxy, (C1-C6) lower alkoxy, or (C1-C6) lower alkoxy carbonyl, carboxy, —CONH2, —CONH[(C1-C6) lower alkyl], —CON[(C1-C6) lower alkyl]2; or (2) a 5-membered aromatic (unsaturated) hete

Abstract: This invention comprises antibodies to rapamycin effector proteins, and preparations thereof. Novel Rapamycin-FKBP12 binding proteins, nucleic acids and their fragments are also described, as are related methods and therapeutic uses of the proteins, nucleic acids, and antibodies.

Abstract: This invention comprises novel Rapamycin-FKBP12 binding proteins of mammalian origin for identification, design and synthesis of immunomodulatory, anti-restenosis or anti-tumor agents, as well as fragments of the proteins and the DNA, cDNA, antisense RNA and DNA segments corresponding to the proteins. This invention also comprises methods for isolating the proteins and therapeutic uses related to the proteins.

Abstract: This invention comprises novel Rapamycin-FKBP12 binding proteins of mammalian origin for identification, design and synthesis of immunomodulatory, anti-restenosis or anti-tumor agents, as well as fragments of the proteins and the DNA, cDNA, antisense RNA and DNA segments corresponding to the proteins. This invention also comprises methods for isolating the proteins and therapeutic uses related to the proteins.

Abstract: This invention relates to new compounds selected from those of the general formula (I), or a pharmaceutically acceptable salt, ester or prodrug form thereof: wherein D, E and G are N or CH, which serve as vasopressin agonists and are useful in treating disorders such as diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, and the inability to temporarily delay urination and pharmaceutical compositions and methods for same.

Abstract: This invention comprises novel Rapamycin-FKBP12 binding proteins of mammalian origin for identification, design and synthesis of immunomodulatory, anti-restenosis or anti-tumor agents, as well as fragments of the proteins and the DNA, cDNA, antisense RNA and DNA segments corresponding to the proteins. This invention also comprises methods for isolating the proteins and therapeutic uses related to the proteins.

Abstract: The present invention provides compounds of the general formula: wherein Y is a moiety selected independently, from NH or —(CH2)n— wherein n is 1; m is an integer from 1 to 2; and the moiety represents: (1) a 5-membered aromatic (unsaturated) heterocyclic ring having one nitrogen (wherein A is nitrogen, and B and C are CH), (2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen (wherein A is carbon, B is nitrogen, and C is —CH—CH—), (3) a 6-membered aromatic (unsaturated) ring (wherein A is carbon, B is CH, and C is —CH—CH—); as well as methods and pharmaceutical compositions utilizing these compounds for the treatment of disorder which may be remedied or alleviated by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, or temporary delay of urination.

Abstract: The present invention provides compounds of the general formula: wherein Y is a moiety selected independently, from NH or —(CH2)n— wherein n is 1; m is an integer from 1 to 2; and the moiety represents: (1) a 5-membered aromatic (unsaturated) heterocyclic ring having one nitrogen (wherein A is nitrogen, and B and C are CH), (2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen (wherein A is carbon, B is nitrogen, and C is —CH—CH—), (3) a 6-membered aromatic (unsaturated) ring (wherein A is carbon, B is CH, and C is —CH—CH—); as well as methods and pharmaceutical compositions utilizing these compounds for the treatment of disorder which may be remedied or alleviated by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, or temporary delay of urination.

Abstract: This invention relates to tricyclic non-peptide vasopressin antagonists which are useful in treating conditions where decreased vasopressin levels are desired, such as in congestive heart failure, in disease conditions with excess renal water reabsorption and in conditions with increased vascular resistance and coronary vasoconstriction, the compounds having the general structure: ##STR1##

Abstract: This invention provides compounds of formula I having the structure ##STR1## wherein R is (CH.sub.2).sub.n COOR.sup.4 ;R.sup.1 is hydrogen, alkyl, alkenyl, alkynyl, alkylcycloalkyl, and alkoxyalkyl;R.sup.4 is hydrogen or alkyl;R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, arylalkoxy, fluoroalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, nitro, --SCF.sub.3, --COR.sup.3, alkanoyloxy, hydroxy, trifluoromethyl, amino, alkylamino, dialkylamino, alkylamido, or alkylsulfonamido; wherein at least one of R.sup.5, R.sup.6, R.sup.7, or R.sup.8 is cyano;R.sup.3 is alkyl, hydroxy, alkoxy, amino, alkylamino;X is --O-- or --C--; andn=1-4or a pharmaceutically acceptable salt thereof, which are useful in the treatment of arthritic disorders, colorectal cancer, and Alzheimer's disease.

Abstract: This invention provides compounds of formula I having the structure ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are, each, independently, hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aralkoxy, trifluroalkoxy, alkanoyloxy, hydroxy, halo, trifluoromethyl, cyano, amino, mono- or di-alkylamino, alkanamido, or alkanesulfonamido;R.sub.5 is hydrogen, alkyl, alkenyl, alkoxyalkyl or alkylcycloalkyl;R.sub.6 is hydrogen, alkyl or alkenyl;X is oxygen or carbon;A is oxygen or NZ;Z is hydroxyl, alkoxy, aryloxy, carboxyalkyloxy of 2-7 carbon atoms, arylamino, or alkylsulfonyamino of 1-6 carbon atoms;or a pharmaceutically acceptable salt thereof, which are useful in the treatment of arthritic disorders, colorectal cancer, and Alzheimer's disease.

Abstract: This invention provides compounds of formula I having the structure ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are, each, independently, hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aralkoxy, trifluroalkoxy, alkanoyloxy, hydroxy, halo, trifluoromethyl, cyano, amino, mono- or di-alkylamino, alkanamido, or alkanesulfonamido;R.sub.5 is hydrogen, alkyl, alkenyl, alkoxyalkyl or alkylcycloalkyl;R.sub.6 is hydrogen, alkyl or alkenyl;X is oxygen or carbon;A is oxygen or NZ;Z is hydroxyl, alkoxy, aryloxy, carboxyalkyloxy of 2-7 carbon atoms, arylamino, or alkylsulfonyamino of 1-6 carbon atoms;or a pharmaceutically acceptable salt thereof, which are useful in the treatment of arthritic disorders, colorectal cancer, and Alzheimer's disease.

Abstract: A compound of the following structure: ##STR1## wherein R.sub.8 =H: R.sub.1 =alkyl, cycloalkyl, arylalkyl, aryl;R.sub.2 =cycloalkyl, aryl, C.sub.3 -C.sub.10 alkyl;X,Y=O, S(O).sub.n, NH;Z=CO.sub.2 R.sub.3, C(O)CO.sub.2 R.sub.3, CH(OH)CO.sub.2 R.sub.3, CHFCO.sub.2 R.sub.3, CF.sub.2 CO.sub.2 R.sub.3, CONR.sub.3 R.sub.4, CONR.sub.3 OR.sub.4, CONR.sub.3 NR.sub.4 R.sub.5, 1-tetrazole, C(O)CONR.sub.3 R.sub.4, CH(OH)CONR.sub.3 R.sub.4, CF.sub.2 CONR.sub.3 R.sub.4R.sub.3, R.sub.4, R.sub.5 =hydrogen, alkyl, aryl, aryalkyl, cycloalkyl, or fluoroalkyl;halo=Cl, Br, or I;fluoroalkyl=CF.sub.3, CHF.sub.2, CH.sub.2 F, CH.sub.2 CF.sub.3, C.sub.2 F.sub.5 ;cycloalkyl=C.sub.3 -C.sub.6 cycloalkyl;arylalkyl=C.sub.1 -C.sub.4 alkyl aryl;aryl=phenyl, furanyl, thienyl, or pyridyl; andn=0-2;or pharmaceutically acceptable salts thereof, useful in the treatment of asthma, and allergic and inflammatory diseases, as well as methods of treatment and pharmaceutical compositions utilizing the same.

Abstract: A compound of the following structure: ##STR1## wherein, when R.sub.8 =H: R.sub.1 =alkyl, cycloalkyl, arylalkyl, aryl;R.sub.2 =cycloalkyl, aryl, C.sub.3 -C.sub.10 alkyl;X,Y=O, S(O).sub.n, NH;Z=CHO, CO.sub.2 R.sub.3, CONHR.sub.4 R.sub.5, CN, COR.sub.6, H, halo, HCN, NHCONR.sub.4 R.sub.5, CONR.sub.4 OR.sub.5, CONR.sub.4 NR.sub.5 R.sub.6, 1-tetrazole, S(O).sub.n OH, S(O).sub.n NR.sub.3 R.sub.4, C.dbd.NOH, C(.dbd.N(OH)NH.sub.2, OCONR.sub.7 R.sub.6, P(O)(OR.sub.4).sub.2, C(.dbd.N(YR.sub.3))R.sub.4, NH.sub.2, SH, OH, OS(O).sub.2 R.sub.3, C(.dbd.NYC(.dbd.O)R.sub.3)R.sub.4, C(O)CO.sub.2 R.sub.3, C(O)CONR.sub.3 R.sub.4, CH(OH)CO.sub.2 R.sub.3, CHFCO.sub.2 R.sub.3, CF.sub.2 CO.sub.2 R.sub.3, CH(OH)CONR.sub.3 R.sub.4, CF.sub.2 CONR.sub.3 R.sub.4, C.dbd.NNH.sub.2, C(.dbd.NOC(.dbd.O)R.sub.3)R.sub.4, C(.dbd.NNHC(.dbd.O)R.sub.3)R.sub.4, C(.dbd.NOH)R.sub.3, C(.dbd.NNR.sub.3)R.sub.4, NHC(.dbd.O)R.sub.6 or C(O)CONH.sub.2 ;R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.

Abstract: This invention provides a method of prophylactically preventing the onset, preventing the development, and arresting the progression of insulin dependent diabetes mellitus in a mammal by administering an effective amount of rapamycin either alone or in combination with insulin.