1628759-75-0Relevant academic research and scientific papers
Difluoromethylene at the γ-Lactam α-Position Improves 11-Deoxy-8-aza-PGE1 Series EP4 Receptor Binding and Activity: 11-Deoxy-10,10-difluoro-8-aza-PGE1 Analog (KMN-159) as a Potent EP4 Agonist
Barrett, Stephen D.,Holt, Melissa C.,Kramer, James B.,Germain, Bradlee,Ho, Chi S.,Ciske, Fred L.,Kornilov, Andrei,Colombo, Joseph M.,Uzieblo, Adam,O'Malley, James P.,Owen, Thomas A.,Stein, Adam J.,Morano, Maria I.
, p. 4731 - 4741 (2019/05/21)
A series of small-molecule full agonists of the prostaglandin E2 type 4 (EP4) receptor have been generated and evaluated for binding affinity and cellular potency. KMN-80 and its gem-difluoro analog KMN-159 possess high selectivity relative to other prostanoid receptors. Difluoro substitution is positioned alpha to the lactam ring carbonyl and results in KMN-159's fivefold increase in potency versus KMN-80. The two analogs exhibit electronic and conformational variations, including altered nitrogen hybridization and lactam ring puckering, that may drive the observed difluoro-associated increased potency within this four-compound series.
LACTAM COMPOUNDS AS EP4 RECEPTOR-SELECTIVE AGONISTS FOR USE IN THE TREATMENT OF EP4-MEDIATED DISEASES AND CONDITIONS
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Paragraph 0508-0509, (2016/05/02)
Disclosed herein are compounds of formula (I) wherein L1, L2, L3, L4, R1, R4, R5, R6, and s are as defined in the specification. Compounds of formula (I) are EP4 agonists useful in the treatment of glaucoma, osteoporosis, bone fracture, periodontal bone loss, orthopedic implant, alopecia, neuropathic pain, and related disorders. Pharmaceutical compositions and methods of treating conditions or disorders are also described.
LACTAM COMPOUNDS AS EP4 RECEPTOR-SELECTIVE AGONISTS FOR USE IN THE TREATMENT OF EP4-MEDIATED DISEASES AND CONDITIONS
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Paragraph 0535-0537; 0679, (2016/10/09)
Disclosed herein are compounds of formula (I) wherein L 1 , L 2 , L 3 , L 4 , R 1 , R 4 , R 5 , R 6 , and s are as defined in the specification. Compounds of formula (I) are EP 4 agonists useful in the treatment of glaucoma, osteoporosis, bone fracture, periodontal bone loss, orthopedic implant, alopecia, neuropathic pain, and related disorders. Pharmaceutical compositions and methods of treating conditions or disorders are also described.
METHODS, SYSTEMS, AND COMPOSITIONS FOR PROMOTING BONE GROWTH
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Paragraph 01041-01042, (2015/02/02)
The present invention relates to novel bone compositions for locally delivering a therapeutic agent to the site of a bone defect. Therapeutic agents may promote repair of the bone defect and/or treat conditions or disorders such as pain, inflammation, cancer, and infection. The compositions include calcium phosphate cements and a demineralized bone matrix or a collagen sponge. The compositions are useful for implantation in a patient at the site of a bone defect.
