Eli Lilly and Company

Larry C Blaszczak

John E Munroe

Douglas O Spry

Lowell D Hatfield

Jack W Fisher

Michael Robert Wiley

Jan R Turner

Qing Shi

Scott Martin Sheehan

Michael Alan Robertson

Shon Roland Pulley

Brian Morgan Watson

Michael Scott VanNieuwenhze

Kathleen Ann Taylor

Neil Thomas Blackburn

Paul Luther Skatrud

Robin D Cooper

William Joseph Hornback

Stjepan P Kukolja

John Robert Rizzo

James A Aikins

Brian Michael Mathes

Scott C Mauldin

Mohammad Sadegh Zia-Ebrahimi

William Ernest Alborn, Jr

John Astor Cleveland, Jr

Angelika Regina Kraft

Kevin P Lund

Charles Ellis Cohen

Elizabeth Anne Dingess-Hammond

The present invention is directed to compounds of formula (I) or a pharmaceutically acceptable salt thereof; wherein A is (1); X is selected from CH, CF and N; R5 is selected from H, C-Calkyl, C-Cfluoroalkyl, and &#x2014;OR12; R9 is selected from H &#x2014;NR13C(O)R14 and &#x2014;C(O)NR10R11; R12 is selected from H, C-Calkyl and C-Ccycloalkyl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes. 

Pyridine derivatives as dipeptedyl peptidase inhibitors

Provided are synthetic polysaccharide antigens (SPAs) with anti-inflammatory or inflammatory immunomodulatory properties, depending on their structure. Also provided are compositions comprising these SPAs, and methods of using these SPAs and compositions to either prevent or treat inflammatory pathologies, or diseases or conditions susceptible to treatment with inflammatory immunomodulators, by using appropriate SPAs.

Synthetic polysaccharide antigens for immunological intervention in disease

The present invention is directed to compounds of formula (I): or a pharmaceutically acceptable salt thereof; wherein A is (II); X is selected from CH, CF and N, R8 is selected from H, C-Calkyl, aryl, heteroaryl, C-Calkylaryl, C-Calkylheteroaryl, C-Calkyl-O&#x2014;C-Calkyl, C-Chaloalkyl, hydroxy C-Calkyl, &#x2014;C(O)R9 and &#x2014;SOR9, or R7 and R8 combine to form (III), (IV); W is selected from CR1O and CR15, R1O is selected from H, halo, &#x2014;C(O)NR13R14, C-Calkyl, aryl, heteroaryl, C-Calkylaryl, C-Calkylheteroaryl, C-Calkyl-O&#x2014;C-Calkyl and hydroxy C-Calkyl; Het is a N-linked 5-membered heteroaryl ring optionally substituted with 1-3 substituents selected from methoxy, Cl, F, CH, CF, aryl, heteroaryl, C-Calkylaryl or C-Calkylheteroaryl, for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes. 

1-amino linked compounds

The present invention is directed to compounds of formula (I) or a pharmaceutically acceptable salt thereof; wherein A is (xx); X is selected from CH, CF and N, R5 is selected from H, C-Calkyl, C-Cfluoroalkyl, and &#x2014;OR12, R9 is selected from H and &#x2014;C(O)NR1OR1 1, R12 is selected from H, C-Calkyl and C-Ccycloalkyl for use as inhibitors of the DPP-IV enzyme in the treatment or prevention of conditions including Type II diabetes. 

Phenyl compounds and their use in the treatment of Type II diabetes

Provided are natural and synthetic immunomodulatory polymeric antigens (SPAs), compositions containing SPAs, and methods of using these natural and synthetic SPAs and compositions to prevent or treat inflammatory pathologies.

Immunomodulatory polymeric antigens for treating inflammatory pathologies

The stereospecific synthesis of a glycopeptide using a triply orthogonal protection scheme is described, in particular, the synthesis of N-acetylglucosaminyl-&#x3b2;-[1,4]-N-acetylmuramylmonopeptide and derivatives thereof. The glycopeptide is useful for the preparation of GMDP and related compounds having a glucosaminyl-&#x3b2;-[1,4]-N-acetylmuramic acid disaccharide core.

Glycopeptide and preparation thereof

A process is described for preparing a substrate for the transglycosylase enzymes of bacterial cell wall biosynthesis. The chemical synthesis makes available a sustainable and substantially pure source of supply of lipid II, including analogs thereof, that may be used in the identification of new therapeutic agents capable of disrupting steps in bacterial cell wall biosynthesis.

Process for preparing lipid II

The invention provides 1,3,4 substituted and bicyclic derivatives of 2-azetidinones and processes therefor. These compounds are valuable intermediates useful in the preparation of 1-carba(dethia)cephalosporin antibiotics.

1,3,4 substituted and bicyclic derivatives of 2-azetidinones and

A method for preparing 2-amino-.beta.-lactams which are substituted by readily-removed protecting groups is provided. According to this invention, an acyl-2-amino-.beta.-lactam is further acylated with a different acyl group and is subsequently treated with base to provide a protected 2-amino .beta.-lactam with a more desirable protecting group.

Bicyclic .beta.-lactam antibiotics

.beta.-lactam antibiotics

The invention provides a free radical process for preparing 1-carba(1-dethia)cephalosporin antibiotics with 2-substituted methylcephalosporin 1,1-dioxides wherein the substituent on the 2-methylene group is a free radical precursor group such as a phenyl or alkylseleno group. The latter dioxides are treated with a free radical initiator, e.g., a trialkyltin hydride or actinic radiation at 40.degree. C. to 150.degree. C. to provide the 1-carba-3-cephem and 1-carba-2-cephem products. The invention also provides free radical compounds formed as intermediates in the process.

Cephalosporin free radical compounds

A method for preparing 2-amino-.beta.-lactams which are substituted by readily-removed protecting groups is provided. According to this invention, an acyl-2-amino-.beta.-lactam is further acylated with a different acyl group and is subsequently treated with base to provide a protected 2-amino .beta.-lactam with allyloxycarbonyl, t-butoxycarbonyl, naphthyloxycarbonyl, trichloroethyloxycarbonyl, p-nitrobenzyloxycarbonyl, benzhydryloxycarbonyl, p-methoxybenzyloxycarbonyl, or o-nitrobenzyloxycarbonyl.

Method of deprotection of 3-amino azetidinones

The invention provides a free radical process for preparing 1-carba(1-dethia)cephalosporin antibiotics represented by the formula ##STR1## wherein R is amino or protected amino, R.sub.1 is H or alkoxy, R.sub.3 is H or alkyl, Z is ##STR2## where R.sub.2 is, e.g., H, halogen, or alkyl, or --CH.sub.2 R.sub.2 ' where R.sub.2 ' is, e.g., hydroxy, methoxy, or heterocyclicthio group, and A is a carboxy-protecting group which comprises heating a 2-substituted-methylcephalosporin 1,1-dioxide of the formula ##STR3## wherein R, R.sub.1, R.sub.3, and A are the same as in the formula above and Y is a free radical precursor group, e.g., C.sub.1 -C.sub.6 --Se--, C.sub.1 -C.sub.6 --S--, or phenyl--Se--; with a free radical initiator, e.g., a trialkyltin hydride, radiation, or a cobalt I salophen. Also provided are free radical compounds formed as intermediates in the process.

Process for 1-carba(dethia) cephalosporins

This invention relates to certain 3-acylamino-4-(2'-substituted or unsubstituted allyl)-azetidinone products of the formula ##STR1## wherein R.sub.12 is an acyl group;

Growing community of inventors

Indianapolis, IN, United States of America

Larry C Blaszczak