Abstract: This invention relates to a series of substituted aromatic ethers of the formula I
wherein ring A and X and Y are defined as in the specification, that exhibit activity as glycine transport inhibitors, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their use for the enhancement of cognition and the treatment of the positive and negative symptoms of schizophrenia and other psychoses in mammals, including humans.
Abstract: The present invention relates to novel screening methods which enable the selection of neurokinin-1 (NK-1) receptor antagonist compounds which do not possess significant inhibitory potency towards cytochrome P450 enzymes, in particular, CYP2D6. The present invention also relates to a method of generating a pharmacophore model for the CYP2D6 inhibitory activity of NK-1 receptor antagonist compounds; to methods for the discovery of molecules that are potential NK-1 receptor antagonist compounds which do not possess significant inhibitory potency towards the CYP2D6 enzyme; to methods of modeling the features of the CYP2D6 pharmacophore useful in selecting NK-1 receptor antagonist molecules which do not possess significant potency towards CYP2D6.
Abstract: Compounds of the formula (I):
wherein A, Y, R, X, R1, R2, R3 and R4 are as defined above are inhibitors of rotamase enzymes in particular FKBP-12 and FKBP-52. The compounds therefore moderate neuronal regeneration and outgrowth and can be used for treating neurological disorders arising from neurodegenerative diseases or other disorders involving nerve damage.
Type:
Grant
Filed:
January 23, 2002
Date of Patent:
May 13, 2003
Assignee:
Pfizer Inc
Inventors:
Mark Ian Kemp, Michael John Palmer, Mark Allen Sanner, Martin James Wythes
Abstract: This invention provides a RP-HPLC method, for the determination of logPoct values, which combines ease of operation and high accuracy, and which has been shown to work for a set of 36 molecules largely comprised of drugs. The general features of the method are: i) compound sparing (≦1 mL of a 30-50 &mgr;g/mL solution needed), ii) rapid determinations (20 minutes on average), iii) low sensitivity to impurities, iv) wide lipophilicity range (6 logPoct units), v) good accuracy, vi) excellent reproducibility. A linear free energy relationship (LFER) analysis, based on solvation parameters, shows that the method encodes the same information obtained from a shake-flask logPoct determination. The value generated via this method is referred to as ElogPoct.
Type:
Grant
Filed:
February 13, 2001
Date of Patent:
April 15, 2003
Assignee:
Pfizer Inc.
Inventors:
Franco Lombardo, Marina Y. Shalaeva, Karl A. Tupper
Abstract: The present invention relates to compounds of the formula 1
and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X1, R1, R2 and R3 are as defined herein. The invention also relates to pharmaceutical compositions containing the above compounds and to methods treating hyperproliferative disorders in mammals by administering the above compounds.
Type:
Grant
Filed:
March 9, 2001
Date of Patent:
April 15, 2003
Assignee:
Pfizer Inc
Inventors:
Eric R. Larson, Mark C. Noe, Thomas G. Gant
Abstract: The invention relates to the use of a cyclic guanosine 3′, 5′-monophosphate phosphodiesterase type five (cGMP PDE V) inhibitor for increasing fecundity in a mammal by one or more of (a) promoting the growth of an oocyte, zygote, blastocyst, embryo and/or foetus, (b) increasing the rate or probability of survival of an embryo and/or foetus and (c) increasing the birth weight of a progeny, or for increasing milk productivity.
Type:
Grant
Filed:
October 18, 2001
Date of Patent:
April 15, 2003
Assignee:
Pfizer, Inc.
Inventors:
Simon Lempriere Westbrook, Johannes Fridrich Zanzinger
Abstract: The present invention concerns methods, pharmaceutical compounds, and compositions for stimulating neuroite outgrowth in nerve cells leading to nerve regeneration. These methods, compounds and compositions inhibit rotamase enzyme activity associated with binding proteins.
Type:
Grant
Filed:
December 1, 2000
Date of Patent:
April 8, 2003
Assignee:
Pfizer Inc.
Inventors:
Chuangxing Guo, Liming Dong, Xinjun J. Hou, Darin Vanderpool, Jesus Ernest Villafranca
Abstract: A method of treating hyperproliferation diseases in mammals in need of such treatment, which method includes administering to said mammal a therapeutically effective amount of a compound of the formula:
or a pharmaceutically acceptable salt, hydrate or prodrug thereof, wherein R1, R2, R3, R4, W, X, Y, Z and t are as defined herein.
Type:
Grant
Filed:
April 13, 2000
Date of Patent:
April 1, 2003
Assignee:
Pfizer INC
Inventors:
Steven W. Goldstein, Kelly P. Longo, Bernard Hulin
Abstract: The invention relates to compounds of the formula 1
and to pharmaceutically acceptable salts and solvates thereof, wherein A, X, R1, R3 and R4 are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals with administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.
Type:
Grant
Filed:
April 12, 2001
Date of Patent:
April 1, 2003
Assignee:
Pfizer Inc
Inventors:
John Charles Kath, Norma Jacqueline Tom, Zhengyu Liu, Eric David Cox, Joel Morris, Samit Kumar Bhattacharya
Abstract: The present invention provides diazabicyclooctane derivatives of formula (I):
and pharmaceutically acceptable salts thereof, wherein the group represents
R1 and R2 are selected independently from H, (C1-C6)alkyl, (C1-C6)fluoroalkyl, halogen (e.g., F.
Type:
Grant
Filed:
August 1, 2001
Date of Patent:
March 11, 2003
Assignee:
Pfizer Inc
Inventors:
Anton Franz Joseph Fliri, Randall James Gallaschun
Abstract: CRF antagonists of Formulas I-V, wherein the B group in the Formulas contains an oxime
The variables in the Formulas have the meanings described herein.
Abstract: The invention described herein relates to the use of calcium channel blockers such as amlodipine in the treatment of renal disease in normotensive animals. Also described are new unit doses of amlodipine suitable for the treatment of renal disease in normotensive cats.
Abstract: The present invention relates to polynucleotide molecules comprising nucleotide sequences encoding an aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of S. avermitilis. The present invention further relates to vectors, host cells, and mutant strains of S. avermitilis in which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.
Type:
Grant
Filed:
January 22, 2001
Date of Patent:
January 28, 2003
Assignees:
Pfizer, Inc., Pfizer Products, Inc.
Inventors:
Kim J. Stutzman-Engwall, Hamish McArthur, Yoshihiro Katoh
Abstract: The present invention relates to polynucleotide molecules comprising nucleotide sequences encoding the aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of Streptomyces avermitilis. The present invention further relates to vectors, host cells, and mutant strains of Streptomyces avermitilis in which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.
Type:
Grant
Filed:
January 22, 2001
Date of Patent:
January 21, 2003
Assignees:
Pfizer Inc., Pfizer Products Inc.
Inventors:
Kim J. Stutzman-Engwall, Hamish McArthur, Yoshihiro Katoh
Abstract: A compound of the formula
wherein R1-R9 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, restenosis, periodontal disease, epidemrolysis bullosa, scleritis and other disease characterized by matrix metalloproteinase activity, as well as AIDS, sepsis, septic shock and other diseases involving the production of TNF.
Abstract: The invention provides a compound of formula (I):
and its pharmaceutically acceptable salts, wherein
R is halo C2-C8 alkenyl or halo C2-C8 alkynyl;
R1 is hydrogen, halo or C1-C6 alkoxy;
or R and R1, together with the two carbon atoms to which they are attached, form a C4-C6 cycloalkyl or a C4-C6 oxacycloalkyl ring wherein said ring may be optionally substituted by one or more substituents selected from the group consisting of halo, C1-C6 alkyl and halo C1-C6 alkyl;
X is C1-C6 alkoxy, halo C1-C6 alkoxy, phenoxy or halo; and
Ar is phenyl optionally substituted by halo.
These compounds are useful in the treatment of a gastrointestinal disorder; a central nervous system (CNS) disorder; an inflammatory disease; emesis; urinary incontinence; pain; migraine; sunburn; diseases, disorders and adverse conditions caused by Heliobacter pylori; or angiogenesis especially CNS disorders in a mammalian subject, especially humans.
Abstract: Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in the affected joint of a mammal is accomplished by administering a chondroprotective compound of Formula (I):
where A is hydroxy, (C1-C4)alkoxy, amino, hydroxy-amino, mono-(C1-C2)alkylamino, di-(C1-C2)alkylamino; X and Y are independently H or (C1-C2)alkyl; and n is 1 or 2; R6 is halogen, (C1-C3)alkyl, trifluoromethyl, or nitro; R9 is H; (C1-C2)alkyl; phenyl or phenyl-(C1-C2)alkyl, where phenyl is optionally mono-substituted by fluoro or chloro; —C(═O)—R, where R is (C1-C2)alkyl or phenyl, optionally mono-substituted by fluoro or chloro; or —C(═O)—O—R′, where R1 is (C1-C2)alkyl.
This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration.
Type:
Grant
Filed:
April 1, 1999
Date of Patent:
January 14, 2003
Assignee:
Pfizer, Inc.
Inventors:
Nigel A. Evans, Carolyn R. Kilroy, Kristin M. Lundy, Jean-Pierre Pelletier, Anthony P. Ricketts
Abstract: The present invention relates to compounds of the formula I,
wherein Z1, Z2, X, Q, R1, R2 and R3 are defined as in the specification, pharmaceutical compositions containing such compounds the use of such compounds to treat neurological and gastrointestinal disorders.
Type:
Grant
Filed:
August 6, 1999
Date of Patent:
January 7, 2003
Assignee:
Pfizer Inc
Inventors:
Spiros Liras, Martin P. Allen, Barbara E. Segelstein
Abstract: The invention provides isolated polynucleotide molecules, including plasmids; viral vectors; and transfected host cells that comprise a DNA sequence encoding an infectious RNA sequence encoding a North American PRRS virus; and also North American PRRS viruses encoded thereby. The invention further provides isolated infectious RNA molecules encoding a North American PRRS virus. The invention also provides isolated polynucleotide molecules, infectious RNA molecules, viral vectors, and transfected host cells encoding genetically-modified North American PRRS viruses; and genetically-modified North American PRRS viruses encoded thereby. The invention also provides vaccines comprising such plasmids, RNA molecules, viral vectors, and North American PRRS viruses, and methods of using these vaccines in swine and in other animals. Also provided are isolated polynucleotide molecules, viral vectors, and transfected host cells that comprise a nucleotide sequence encoding a peptide of a North American PRRS virus.
Type:
Grant
Filed:
December 22, 1999
Date of Patent:
December 31, 2002
Assignee:
Pfizer Inc.
Inventors:
Jay G. Calvert, Michael G. Sheppard, Siao-Kun W. Welch