Disclosed are imidazo[1,2-b]pyrimido[4,5-d]pyridazin-5(6H)-one compounds, specifically represented by the Formula I: ##STR00001##
or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R.sub.1-R.sub.5 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.

Compounds having the general formula (I) ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are as described herein, compositions including the compounds and methods of using the compounds.

The present invention relates to sulfonamides and related compounds which are inhibitors of PARG and are useful in the treatment of cancer.

The present invention relates to sulfonamides and related compounds which are inhibitors of PARG and are useful in the treatment of cancer.

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a α5-containing GABA.sub.A receptor agonist (e.g., a α5-containing GABA.sub.A receptor positive allosteric modulator) as described herein in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction.

The subject matter of the invention relates to novel sulfonamide derivatives of 7-methyl-5-phenyl-pyrazolo[4,3-c]tetrazolo[4,5-b] [1,2,4]triazine comprising L-proline or 4-hydroxy-L-proline in the sulfonamide group. The novel compounds exhibit cytostatic activity against gastric cancer cell (AGS) and colorectal cancer cell (DLD-1 and HT-29) lines and may be used as novel medicaments which have anticancer action. The subject matter of the invention also relates to a method of manufacturing such derivatives, as well as uses thereof and a pharmaceutical composition comprising the same.

##STR00001##

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Triazabicylodecene can effectively n-dope a variety of organic semiconductors, including PCBM, thus increasing in-plane conductivities. We synthesized a series of TBD-based n-dopants via an N-alkylation reaction and studied the effect of various alkyl chains on the physical and device properties of the dopants. Combining two TBD moieties on a long alky chain gave a solid dopant, 2TBD-C10, with high thermal stability above 250° C. PCBM films doped by 2TBD-C10 were the most tolerant to thermal annealing and reached in-plane conductivities of 6.5×10.sup.−2 S/cm. Furthermore, incorporating 2TBD-C10 doped PCBM as the electron transport layer (ETL) in methylammonium lead triiodide (MAPbI.sub.3) based photovoltaics led to a 23% increase in performance, from 11.8% to 14.5% PCE.

Triazabicylodecene can effectively n-dope a variety of organic semiconductors, including PCBM, thus increasing in-plane conductivities. We synthesized a series of TBD-based n-dopants via an N-alkylation reaction and studied the effect of various alkyl chains on the physical and device properties of the dopants. Combining two TBD moieties on a long alky chain gave a solid dopant, 2TBD-C10, with high thermal stability above 250° C. PCBM films doped by 2TBD-C10 were the most tolerant to thermal annealing and reached in-plane conductivities of 6.5×10.sup.−2 S/cm. Furthermore, incorporating 2TBD-C10 doped PCBM as the electron transport layer (ETL) in methylammonium lead triiodide (MAPbI.sub.3) based photovoltaics led to a 23% increase in performance, from 11.8% to 14.5% PCE.

The disclosure relates to methods of administering comprising administration of inhibitors of phosphodiesterase 1 (PDE1) for the treatment and/or prophylaxis of renal disorders, such as chronic kidney disease. Related compounds and methods of making are further defined.