Fibrogen, Inc.

Burroughs Wellcome Co.

The General Hospital Corporation

David A Yeowell

Michael P Arend

Michael D Thompson

Jung Min Park

Claudia Witschi

Michael Martinelli

Roy A Swaringen, Jr

Thomas B Neff

William Usinger

Qingjian Wang

Al Y Lin

Noelynn A Oliver

Hassan A El-Sayad

John J Savarese

James C Wisowaty

William R Usinger

Michael John Martinelli

Ai Y Lin

The present disclosure relates to crystalline solid forms of [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, the process of preparing the forms, and pharmaceutical compositions and methods of use thereof.

Crystalline forms of a prolyl hydroxylase inhibitor

The present invention relates to antibodies that bind to CTGF. The antibodies are particularly directed to regions of CTGF involved in biological activities associated with fibrosis. The invention also relates to methods of using the antibodies to treat disorders associated with CTGF including localized and systemic fibrotic disorders including those of the lung, liver, heart, skin, and kidney.

Connective tissue growth factor antibodies

The present invention relates to antibodies that bind to a portion of the Von Willebrand's factor (VWC) domain of connective tissue growth factor (CTGF). The antibodies are particularly directed to regions of CTGF involved in biological activities associated with fibrosis. The invention also relates to methods of using the antibodies to treat disorders associated with CTGF including localized and systemic fibrotic disorders including those of the lung, liver, heart, skin, and kidney.

Antibodies that bind to a portion of the VWC domain of connective tissue growth factor

Neuromuscular blocking agents of formula (1) which are useful as skeletal muscle relaxants during surgery are disclosed. ##STR1## and X is an anion, preferably pharmaceutically acceptable.

Novel compounds

Long duration muscle relaxant compound of formula (I) ##STR1## and its use in producing muscle relaxation in mammals including man.

Long duration neuromuscular blocking agents

In the synthesis of calcium leucovorin (calcium 5-formyl-5,6,7,8-tetrahydrofolate), the use of an amine base in the conversion of anhydroleucovorin (5,10-methenyl-5,6,7,8-tetrahydrofolic acid) to leucovorin unexpectedly results in a pure (USP) product directly from the reaction mixture.

Synthesis of leucovorin

This invention provides the neuromuscular blocking agents of formula (I): ##STR1## where B and C are each a group of formula (II) and are meta or para to one another: ##STR2## wherein D is CH.sub.2 CH.sub.2 or CH.dbd.CH (preferably trans); Y is alkyl of 1-4 carbon atoms (methyl, ethyl, propyl or butyl); E and F and H or OCH.sub.3 ; X.sup.- is an anion, preferably pharmaceutically acceptable; and the substituted benzyl and substituted propyl groups are in a trans relationship relative to each other in the nitrogen-containing ring. Methods for preparing the compounds, pharmaceutical formulations containing the compounds, and their use are also described.

Method of preparing isomers of bis isoquinolinium compounds

Benzyl cyanoacetals of formula: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are the same or different and each is a halogen or a hydrogen atom, an alkoxy group, an alkyl group, or a dialkylamino group; R.sup.4 is an alkoxycarbonyl group, or an aldehyde group; and R.sup.5 is an alkyl group; the alkyl or alkoxy groups each having from 1 to 4 carbon atoms, and their use as intermediates in the preparation of antibacterial 2,4-diamino-5-benzylpyrimidines. They are prepared from a reaction between an orthoester and an .alpha.-substituted-.beta.-benzylpropionitrile and then the resulting cyanoacetal is converted to the benzylpyrimidine by reaction with guanidine.

Growing community of inventors

Chapel Hill, NC, United States of America

David A Yeowell