99337-98-1

Usage

Uses

Used in Pharmaceutical Industry:
2-(TRANS-4-HYDROXYCYCLOHEXYL)-1H-ISOINDOLE-1,3(2H)-DIONE is used as an impurity in Pramipexole (P700755), a dopamine-D2-receptor agonist, for the early treatment of Parkinson's disease and restless legs syndrome. Its presence as an impurity is significant in the context of drug development and quality control, ensuring the safety and efficacy of the medication.

InChI:InChI=1/C14H15NO3/c16-10-7-5-9(6-8-10)15-13(17)11-3-1-2-4-12(11)14(15)18/h1-4,9-10,16H,5-8H2/t9-,10-

Upstream product

• 22509-74-6 N-ethoxycarbonylphthalimide 
• 27489-62-9 trans-4-hydroxycyclohexylamine 
• 85-44-9 phthalic anhydride 
• 50910-54-8 trans-4-aminocyclohexanol hydrochloride 

Downstream Products

• 478832-23-4 cis-4-nitrobenzoic acid 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)cyclohexyl ester 
• 948304-18-5 cis-2-[4-(4-bromophenoxy)cyclohexyl]isoindole-1,3-dione 
• 948304-19-6 cis-2-[4-(4-methoxyphenoxy)cyclohexyl]isoindole-1,3-dione 
• 948304-20-9 cis-2-[4-(4-nitrophenoxy)cyclohexyl]isoindole-1,3-dione 
• 885012-39-5 cis-2-[4-(4-fluoro-phenoxy)-cyclohexyl]-isoindole-1,3-dione 
• 948304-22-1 cis-2-[4-(3,5-difluorophenoxy)cyclohexyl]isoindole-1,3-dione 
• 948304-23-2 cis-4-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)cyclohexyloxy]benzoic acid ethyl ester 
• 948304-25-4 cis-2-[4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)cyclohexyloxy]benzoic acid ethyl ester 
• 847416-23-3 2-((1R,4R)-4-((tert-butyldimethylsilyl)oxy)cyclohexyl)isoindoline-1,3-dione 
• 1388893-50-2 trans-1-(pyrrolidin-1-yl)-2-[(4-[7-thia-9,11-diazatricyclo[6.4.0.0(2,6)]dodeca-1⁽⁸⁾,2⁽⁶⁾,9,11-tetraen-12-yloxy]cyclohexyl)amino]ethan-1-one 
• 1388893-51-3 trans-2-[[2-oxo-2-(pyrrolidin-1-yl)ethyI](4-[7-thia-9,11-diazatricyclo[6.4.0.0(2,6)]dodeca-1⁽⁸⁾,2⁽⁶⁾,9,11-tetraen-12-yloxy]cyclohexyl)amino]-1-(pyrrolidin-1-yl)ethan-1-one 
• 1394012-04-4 C₂HF₃O₂*C₂₀H₁₉ClF₃N₃O₄ 
• 1394012-00-0 cis-4-nitrobenzoic acid 4-[3-(4-chloro-3-trifluoromethylphenyl)ureido]cyclohexyl ester 
• 1394012-01-1 cis-1-(4-chloro-3-trifluoromethylphenyl)-3-(4-hydroxycyclohexyl)urea 

Relevant academic research and scientific papers

Pharmacological characterization of a new series of carbamoylguanidines reveals potent agonism at the H2R and D3R

Even today, the role of the histamine H2 receptor (H2R) in the central nervous system (CNS) is widely unknown. In previous research, many dimeric, high-affinity and subtype-selective carbamoylguanidine-type ligands such as UR-NK22 (5, pKi = 8.07) were reported as H2R agonists. However, their applicability to the study of the H2R in the CNS is compromised by their molecular and pharmacokinetic properties, such as high molecular weight and, consequently, a limited bioavailability. To address the need for more drug-like H2R agonists with high affinity, we synthesized a series of monomeric (thio)carbamoylguanidine-type ligands containing various spacers and side-chain moieties. This structural simplification resulted in potent (partial) agonists (guinea pig right atrium, [35S]GTPγS and β-arrestin2 recruitment assays) with human (h) H2R affinities in the one-digit nanomolar range (pKi (139, UR-KAT523): 8.35; pKi (157, UR-MB-69): 8.69). Most of the compounds presented here exhibited an excellent selectivity profile towards the hH2R, e.g. 157 being at least 3800-fold selective within the histamine receptor family. The structural similarities of our monomeric ligands to pramipexole (6), a dopamine receptor agonist, suggested an investigation of the binding behavior at those receptors. The target compounds were (partial) agonists with moderate affinity at the hD2longR and agonists with high affinity at the hD3R (e.g. pKi (139, UR-KAT523): 7.80; pKi (157, UR-MB-69): 8.06). In summary, we developed a series of novel, more drug-like H2R and D3R agonists for the application in recombinant systems in which either the H2R or the D3R is solely expressed. Furthermore, our ligands are promising lead compounds in the development of selective H2R agonists for future in vivo studies or experiments utilizing primary tissue to unravel the role and function of the H2R in the CNS.

Cobalt-Catalyzed Desymmetric Isomerization of Exocyclic Olefins

Chiral cyclic olefins, 1-methylcyclohexenes, are versatile building blocks for the synthesis of pharmaceuticals and natural products. Despite the prevalence of these structural motifs, the development of efficient synthetic methods remains an unmet challenge. Herein we report a novel desymmetric isomerization of exocyclic olefins using a series of newly designed chiral cobalt catalysts, which enables a straightforward construction of chiral 1-methylcyclohexenes with diversified functionalities. The synthetic utility of this methodology is highlighted by a concise and enantioselective synthesis of a natural product, β-bisabolene. The versatility of the reaction products is further demonstrated by multifarious derivatizations.

POLYCYCLIC INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)

The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma, melanoma, multiple myeloma, breast cancer, Ewing' s sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7), cyclin-dependent kinase 12 (CDK12), or cyclin-dependent kinase 13 (CDK13)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

IRAK INHIBITORS AND USES THEREOF

The present invention relates to compounds and methods useful for inhibiting one or more interleukin-l receptor-associated kinases ("IRAK"). In some embodiments, a provided compound inhibits IRAK-1 and IRAK-4. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

SUBSTITUTED PYRROLOTRIAZINES AS PROTEIN KINASE INHIBITORS

The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) pyrrolotriazines inhibit protein kinase activity thereby making them useful as anticancer agents.

COMPOUNDS WHICH HAVE ACTIVITY AT M1 RECEPTOR AND THEIR USES IN MEDICINE

Compounds of formula (I) or a salt thereof are provided: wherein R4, R5, R6, Q, A, Y and R are as defined in the description. Uses of the compounds as medicaments and in the manufacture of medicaments for treating psychotic disorders, cognitive impairments and Alzheimer's Disease are disclosed. The invention further discloses pharmaceutical compositions comprising the compounds.

BENZIMIDAZOLES WHICH HAVE ACTIVITY AT M1 RECEPTOR AND THEIR USES IN MEDICINE

Compounds of formula (I), salts and solvates are provided: formula (I), wherein Q, R and R6 are as defined in the claims. Uses of the compounds for therapy, for example in the treatment of psychotic disorders and cognitive impairment, are also disclosed.

Orally bioavailable potent soluble epoxide hydrolase inhibitors

A series of N,N′-disubstituted ureas having a conformationally restricted cis- or trans-1,4-cyclohexane α to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activi

4-CYCLOALKYLAMINOPYRAZOLO PYRIMIDINE NMDA/NR2B ANTAGONISTS

Compounds represented by Formula (I): or pharmaceutically acceptable salts thereof, are effective as NMDA/NR2B antagonists useful for treating neurological conditions such as, for example, pain, Parkinson's disease, Alzheimer's disease, epilepsy, depression, anxiety, ischemic brain injury including stroke, and other conditions.

Binding of O-alkyl derivatives of serotonin at human 5-HT1Dβ receptors

In humans, 5-HT1D serotonin receptors represent terminal autoreceptors, and there is some evidence that 5-HT1D ligands may be useful in the treatment of migraine. The most widely used 5-HT1D agonist is sumatriptan; however, this agent reportedly displays little selectivity for 5-HT1D versus 5-HT1A receptors. To identify novel serotonergic agents with enhanced 5-HT1D versus 5-HT1A selectivity, we attempted to take advantage of possible differences in the regions of bulk tolerance associated with the 5-position of the 5-HT binding sites for these two populations of receptors. Examination of a series of 5-(alkyloxy)tryptamine derivatives demonstrated that compounds with unbranched alkyl groups of up to eight carbon atoms bind with high affinity at human 5-HT1Dβ receptors (K(i) 300-fold). Branching of the alkyl chain, to 5-[(7,7-dimethylheptyl)oxy]tryptamine (15), results in an agent with somewhat lower affinity (5-HT1Dβ K(i) = 2.3 nM) but with greater (i.e., 400-fold) 5-HT1D versus 5-HT1A selectivity. Replacement of the oxygen atom of 10 with a methylene group (i.e., 20), replacement of the O-proximate methylene with a carbonyl group (i.e., ester 26), or cyclization of the aminoethyl moiety to a carbazole (e.g., 34, 36) or β- carboline (i.e., 37), result in reduced affinity and/or selectivity. None of the compounds examined displayed significant selectivity for 5-HT1Dβ versus 5-HT1Dα sites; nevertheless, compounds 10 (recently shown to behave as a 5- HT1D agonist) and 15 represent the most 5-HT1D versus 5-HT1A selective agents reported to date.