1134-47-0 Usage
Uses
Used in Pharmaceutical Industry:
Baclofen is used as a pharmaceutical secondary reference standard for the determination of the analyte in plasma samples by liquid chromatography tandem mass spectrometry and tablet formulations by UV spectroscopy.
Used in Neurological Applications:
Baclofen is used as a γ-aminobutyric acid receptor B (GABAB) receptor agonist, controlling GABAergic drug to test its protective effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity, its effects on in vivo motor function tests and performance of mutant mice, its excitability effect on dopaminergic (DA) neurons of the ventral tegmental area (VTA), and its effect in reducing dendritic excitability in Purkinje neurons.
Used in Skeletal Muscle Relaxation:
Baclofen is used as a muscle relaxant (skeletal) and a relaxant and antispasmodic agent acting on the skeletal muscle of the spinal cord. It is suitable for treating multiple-sclerosis bone spasms, spinal infection, degenerated muscle spasms, spinal cord trauma, and neoplastic muscle spasms. It is currently the most effective muscle relaxant with the least side effects.
Brand Names:
Kemstro (Schwarz Pharma); Lioresal (Medtronic); Lioresal (Novartis).
Antispasmodic drugs
Baclofen is a γ-aminobutyric acid derivative. It is an antispasmodics class drugs acting on the central nervous system, the brain and spinal cord as a skeletal muscle relaxants and sedatives. It take antispasmodic effect by stimulating receptors to inhibit the release of excitatory amino acids such as glutamic acid, aspartic acid and thereby inhibiting the transfer of single and multi-synaptic reflex in central nervous system, brain and spinal cord. Clinically it has already been used as racemic agent for treating Muscle spasticity since mid-1960s. Recent studies have also found that this product can significantly reduce the symptoms of gastroesophageal reflux and alleviating related symptoms. It can also alleviate the dystonia of children and treat the urination dysfunction caused by central spinal cord injury. In addition, the intrathecal injection therapy of the product in clinical application can further improve the clinical efficacy, and make it possible to adjust drugs dosage which stabilizes the treatment effect. For the past 10 years, the clinical application of central muscle relaxant baclofen has made significant progress, particularly in accumulating a lot of experiences in the neurological rehabilitation treatment of reducing muscular tension and pain alleviation treatment.
Figure 1 Structure of Baclofen
Mechanisms of action
The content of γ-aminobutyric acid (GABA) is very high in the human central nervous system, brain and spinal cord. Its level is 1000 times higher than monoamine such as catecholamines, to higher norepinephrine, and dopamine. It is presented at the highest inside the substantia nigra and globus pallidus. There are about 20% to 40% of the synapses using GABA as neurotransmitter inside the brain. GABA is the major inhibitory neurotransmitter of the central nervous system, brain and spinal cord. However, it is not able to penetrate the blood-brain barrier. GABA can be converted into baclofen by connecting carbon atom to the p-chlorophenyl. In this case, it changes from hydrophilic substance to lipophilic substances, which can then go through the blood-brain barrier. The main effect of this product are stimulating the GABA receptors, inhibiting the release of excitatory amino acids such as aspartic acid, glutamic acid, also cause the efflux of K +, Ca 2+ , which results in hyper-polarization, reducing the transfer single and multi-synaptic reflex, maintaining the normal function of middle-neuronal activity in order to reduce the activity of motor neurons, thereby alleviating skeletal muscle spasticity caused by damage to the pyramidal tract, reducing muscle tension, and promoting sports functional recovery.
The above information is edited by the lookchem of Dai Xiongfeng.
Production process
Chlorobenzaldehyde and ethyl acetoacetate are condensed into chlorobenzene methylene-bis-ethyl acetoacetate. Heat and hydrolyze to obtain chlorophenyl glutaric acid. Use acetic anhydride for dehydration and cyclization to obtain chlorophenyl glutaric anhydride. And then perform amination reaction by concentrated aqueous ammonia to generate chlorophenyl glutaric acid imide. The open the ring, degrade to obtain the final product.
Pharmacokinetics
After oral administration, concentration in plasma reaches a peak in about 1.9h. There is large fluctuation in plasma concentration with the maximum concentration/minimum concentration × 100%: 188-439%. The total clearance rate is about 175mL.min-1, and the apparent renal clearance crisp is the same as that of muscle. The plasma protein binding rate is 35%. The excretion rate of kidney prototype drug is 65%, which is consistent with healthy results. Because renal excretion is the major route of elimination, patients with renal impairment should pay attention to adjust the dose.
Indications
This product is an antispasmodic drug. It inhibits the transmission in spinal cord of mono-synapse multiple synapse. The mechanism is inhibiting the release of excitatory amino acid glutamate and aspartate through stimulating GABA receptor. Thus reduce the increased limbs muscle tension caused by spinal cord lesions, multiple sclerosis, and spinal cord injury. It can be used for treatment of muscle spasms caused by brain and spinal cord diseases or injuries.
Precautions
1. Among the overdose behavior, the depression of central nervous system is the most prominent. Severe poisoning manifestations include seizures, coma, respiratory depression and muscle hypotonia associated with loss of reflexes of the limbs, and also hypotension and low blood pressure sometimes. Strategies for emergence treatment of acute poisoning include respiratory support, gastric lavage, and diuretic. However, there is no special antidote reported. There are some reports that seizures and myoclonic seizures appeared in some patients appear during the recovery period. Epileptic seizure can be treated by diazepam or clonazepam, although these drugs can cause extension of the duration of unconsciousness. Patients of cardiovascular disease should be carefully observed for 1 week to monitor delayed tachycardia and hypertension.
2. Patients who are allergic to the drug, suffering Parkinson's disease, spasms, and the women who are in the first three months of pregnancy are not allowed for using.
3. Patients of hypertension, peptic ulcer disease, cerebrovascular disease and respiratory, issue liver and kidney dysfunction, who have a history of seizures or convulsions, accompanied by mental disorders, schizophrenia or confusion, pregnant and lactating women, drivers or operator of machine should use with caution.
4. Epileptic patients should be controlled of the attack of epilepsy when applying this drug. Also they should do EEG monitoring.
5. Gradually reduce the dosage before the withdrawal, to prevent rebound phenomenon.
Side effects
The main side effects mainly happen at the beginning of treatment when the dose increases too fast, when overdose happens and for elderly patients. It is mainly mild transient symptoms, Patients with historical mental illness and elderly patients with cerebral vascular disease may suffer from an even more severe adverse reaction. During the beginning of treatment, there are often some side effects such as daytime sedation, drowsiness and nausea.
Side effects
Side effects are not a major problem, and they can be
minimized by graduated dosage increases.They include
lassitude, slight nausea, and mental disturbances (in including
confusion, euphoria, and depression). The
drowsiness is less pronounced than that produced by
diazepam—an important therapeutic advantage. Hypotension
has been noted, particularly following overdose.
Elderly patients and patients with multiple sclerosis
may require lower doses and may display increased sensitivity
to the central side effects. Baclofen may increase
the frequency of seizures in epileptics.
Dosage and usage
Oral: adult, Initial amount of 5mg per time, tid, then every increase taking this amount every 3d until it reaches the appropriate dose 30~75mg/d. Take this in 3 times. The dose should not exceed 80 mg/d except in special cases. Gradually reduce the dosage before withdrawal; For children, the initial amount should be 0.3mg/(kg.d), and the maintenance dose should be 0.75~2mg/(kg.d). For children under 10 years-old, the maximum dose should be 2.5mg /(kg.d). The recommended daily amount for maintenance therapy: 1 to 2 years-old, 10~20mg, 2~10 years-old: 30~60mg (maximum 70mg), take it with meal or with milk.
Production method
Chlorobenzaldehyde and ethyl acetoacetate is condensed into chlorobenzene methylene-bis-ethyl acetoacetate. Add heating water for hydrolysis to obtain chlorophenyl glutaric acid. Dehydrate and cyclize to obtain chlorophenyl glutaric anhydride using acetic anhydride. Then perform amination reaction with concentrated aqueous ammonia to generate chlorophenyl glutaric acid imide. The open the ring, degrade to obtain the final product. Detailed procedures as follow: Add 42.25g β-(p-chlorophenyl) glutaric acid imide with stir to 200 mL aqueous solution containing 8.32g of sodium hydroxide. The mixture was heated at 50 °C for 10min, cool to 10-15 °C. Titrate for 200 mL aqueous solution of 40.9g of sodium hydroxide. After 20min, add 38.8g bromine, stir at 20-25 °C for 8h. Use concentrated hydrochloric acid to adjust the pH of the reaction solution to 7, and then precipitate out the fine crystals of i.e. [beta] (p-chlorophenyl) amino-gamma-acid. Re-crystallize in water with m.p. 206-208 °C.
Toxicity grading
highly toxic
Acute toxicity
Oral-rat LD50; 145 mg/kg; Oral-Mouse LD50: 200 mg/kg.
Flammability and hazardous characteristics
Combustible, Burning yields toxic chloride fumes and nitrogen oxides; Patients takes with side effects: low blood pressure, pulse rate decreases, muscle weakness.
Storage Characteristics
ventilation, low-temperature and dry; and Separate from food raw materials for storage.
Extinguishing agent
Dry powder, foam, sand, carbon dioxide, water spray.
Originator
Lioresal,Ciba Geigy,Switz.,1971
Manufacturing Process
42.45 g of β-(p-chlorophenyl)glutaric acid imide are stirred into a solution of
8.32 g of sodium hydroxide in 200 ml of water. The mixture is heated for 10
minutes at 50°C, and the solution thus formed is cooled to 10° to 15°C. At
this temperature there are then added dropwise a solution of 40.9 g of
sodium hydroxide in 200 ml of water and then, in the course of 20 minutes,
38.8 g of bromine. When all has been dropped in, the batch is stirred for 8
hours at 20° to 25°C. The reaction solution is then cautiously adjusted with
concentrated hydrochloric acid to pH 7, whereupon finely crystalline γ-amino-
β-(p-chlorophenyl)butyric acid settles out. To purify it, it is recrystallized from
water. Melting point is 206°to 208°C.
Therapeutic Function
Muscle relaxant
Biological Functions
Baclofen (Lioresal) is the parachlorophenol analogue
of the naturally occurring neurotransmitter γ-aminobutyric
acid (GABA).
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Baclofen is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.
Health Hazard
SYMPTOMS: Symptoms of exposure to Baclofen via ingestion may include drowsiness, insomnia, dizziness, weakness, mental confusion, nausea, constipation, anorexia, urinary retention, impotence, nystagmus, diplopia and incoordination. Ingestion may lead to cholinergic effects and lassitude. It may also lead to ataxia. Other symptoms due to ingestion may include impaired renal function, fatigue, headache, hypotension, urinary frequency, rash, pruritis, ankle edema, excessive perspiration, weight gain, nasal congestion, and rarely, euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, tremor, rigidity, dystonia, blurred vision, strabismus, miosis, mydriasis, dysarthia, epileptic seizure, dyspnea, palpitation, chest pain, syncope, dryness of the mouth, taste disorder, abdominal pain, vomiting, diarrhea, blood in the stools, enuresis, dysuria, inability to ejaculate, nocturia and hematuria. Overexposure through ingestion may result in seizures, and coma with respiratory depression. Aspiration pneumonia is a frequent complication of coma with respiratory depression. Other symptoms due to overdosage may include vomiting, muscular hypotonia, drowsiness, and accommodation disorders. Cyanosis has been reported. Chronic ingestion may result in drowsiness, depression, weakness, anxiety, ataxia, headaches, blurred vision, gastric upset and pruritic skin rashes characterized by urticaria or erythematous macular eruptions. Sudden withdrawal after chronic ingestion may cause auditory and visual hallucinations, anxiety and tachycardia. Seizures may also occur after sudden withdrawal. Abuse may lead to drug dependence.
Fire Hazard
Flash point data for Baclofen are not available. Baclofen is probably combustible.
Biological Activity
Selective GABA B receptor agonist. Skeletal muscle relaxant.
Biochem/physiol Actions
Baclofen, a γ-aminobutyric acid (GABA) analog, possesses myorelaxant properties Being a γ-aminobutyric acid receptor B (GABAB) agonist, baclofen may be involved in the potentiation of dendritic potassium K+?channels. It may be useful in blocking transient lower esophageal sphincter relaxation (TLESR)?in gastroesophageal reflux disease (GERD). Baclofen may also have scope for treating addictive especially, in alcohol use disorder (AUD).
Mechanism of action
Baclofen appears to affect the neuromuscular axis by
acting directly on sensory afferents, γ-motor neurons,
and collateral neurons in the spinal cord to inhibit both
monosynaptic and polysynaptic reflexes. The principal
effect is to reduce the release of excitatory neurotransmitters
by activation of presynaptic GABAB receptors.
This seems to involve a G protein and second-messenger
link that either increases K+ conductance or decreases
Ca++ conductance.
Clinical Use
Baclofen is an agent of choice for treating spinal spasticity
and spasticity associated with multiple sclerosis. It is
not useful for treating spasticity of supraspinal origin.
Doses should be increased gradually to a maximum of
100 to 150 mg per day, divided into four doses.
Safety Profile
Poison by ingestion,subcutaneous and intravenous routes. Human systemiceffects by ingestion: blood pressure lowering, coma,muscle weakness, pulse rate decrease, respiratorydepression. When heated to decomposition it emits toxicfumes of Cl-
Synthesis
Baclofen, 4-amino-3-(4-chlorophenyl)butyric acid (15.3.5), is synthesized in
two ways. According to the first, 4-chlorobenzaldehyde is condensed with two moles of
acetoacetic ester, giving the product (15.3.1), which initially undergoes alkaline hydrolysis
and decarboxylation forming 3-(4-chlorphenyl)glutaric acid (15.3.2). Dehydration of
this gives 3-(4-chlorophenyl)glutaric acid anhydride (15.3.3), and further treatment with
ammonia gives the corresponding glutarimide (15.3.4). Reacting this with an alkaline solution
of a halogen (Hofmann rearrangement) gives baclofen (15.3.6).
Veterinary Drugs and Treatments
Baclofen may be useful to decrease urethral resistance in dogs to
treat urinary retention. It is not recommended for cats.
in vitro
(±)-baclofen dampened cell growth in human hepatocellular carcinoma (hcc) cells in a dose-dependent manner. (±)-baclofen also caused cell cycle arrest at g0/g1 phase without inducing cell death. additionally, (±)-baclofen-evoked hcc cells proliferation was associated with down-regulation of the intracellular camp level, up-regulation of p21waf1 protein expression and its phosphorylation level, which could be reversed by pretreatment with the gabab antagonist, phaclofen, indicating that (±)-baclofen-evoked growth blockade was exerted in a gabab-dependent fashion [1].
in vivo
the mice, subcutaneously injected with bel-7402 cells, were given an intraperitoneal injection of (±)-baclofen 30 mg/kg every day for 30 days. compared with the control, (±)-baclofen remarkably blocked the bel-7402 xenograft tumor growth without causing toxic effects via measuring the relative tumor volume and the mean body weight change in (±)-baclofen-treated groups, which could make (±)-baclofen as an effective and relatively safe potential drug for the treatment of hcc [1].
Drug interactions
Potentially hazardous interactions with other drugs
Anti-arrhythmics: enhanced muscle relaxant effect
with procainamide.
Antidepressants: enhanced muscle relaxant effect
with tricyclics.
Antihypertensives: enhanced hypotensive effect.
Lithium: use with caution.
IC 50
200 nm: a selective agonist of γ-aminobutyric acid metabotropic receptor (b) (gabab).
Metabolism
Baclofen is rapidly and effectively absorbed after oral
administration. It is lipophilic and able to penetrate the
blood-brain barrier.Approximately 35% of the drug is
excreted unchanged in the urine and feces.
references
[1]. wang, t., huang, w., & chen, f. baclofen, a gabab receptor agonist, inhibits human hepatocellular carcinoma cell growth in vitro and in vivo. life sciences. 2008; 82(9-10): 536-541.
Check Digit Verification of cas no
The CAS Registry Mumber 1134-47-0 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,1,3 and 4 respectively; the second part has 2 digits, 4 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1134-47:
(6*1)+(5*1)+(4*3)+(3*4)+(2*4)+(1*7)=50
50 % 10 = 0
So 1134-47-0 is a valid CAS Registry Number.
InChI:InChI=1/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14)/t8-/m1/s1
1134-47-0Relevant articles and documents
Novel approach to the synthesis of (R,S)-baclofen via PD(II)-bipyridine - Catalyzed conjugative addition
Varala, Ravi,Adapa, Srinivas R.
, p. 3743 - 3747 (2006)
Synthesis of (R,S)-baclofen is described starting from N- phthalimidoacetaldehyde. The key step in the synthesis was Pd(II)-bipyridine- catalyzed conjugative addition of 4-chloroboronic acid. Copyright Taylor & Francis Group, LLC.
Structural characterization and Hirshfeld surface analysis of racemic baclofen
Maniukiewicz, Waldemar,Oracz, Monika,Sieroń, Les?aw
, p. 271 - 275 (2016)
The crystal structure of baclofen, (R,S) [4-amino-3-(4-chlorophenyl)butanoic acid], (C10H12ClNO2, Mr = 213.66) has been determined by single crystal X-ray diffraction analysis. The title compound crystallizes in the orthorhombic space group Pbca (No. 61) with a = 9.2704(5), b = 7.0397(4), c = 30.4015(15) ?, V = 1984.0(2) ?3 and Z = 8. The molecules exist as zwitterions, adopting a gauche conformation with respect to the Cα-Cβ bond, and held in a cross-linked chain arrangement by strong N-H?O hydrogen bonds and C-Cl?π interactions. The electrostatic molecular potential as well as the intermolecular interactions of the title compound were analyzed by the Hirshfeld surfaces. The FT-IR spectrum is also reported. The DTA, TG and DTG results indicate that baclofen is stable up to 205 °C.
Photocatalysis Enables Visible-Light Uncaging of Bioactive Molecules in Live Cells
Wang, Haoyan,Li, Wei-Guang,Zeng, Kaixing,Wu, Yan-Jiao,Zhang, Yixin,Xu, Tian-Le,Chen, Yiyun
supporting information, p. 561 - 565 (2019/01/04)
The photo-manipulation of bioactive molecules provides unique advantages due to the high temporal and spatial precision of light. The first visible-light uncaging reaction by photocatalytic deboronative hydroxylation in live cells is now demonstrated. Using Fluorescein and Rhodamine derivatives as photocatalysts and ascorbates as reductants, transient hydrogen peroxides were generated from molecular oxygen to uncage phenol, alcohol, and amine functional groups on bioactive molecules in bacteria and mammalian cells, including neurons. This effective visible-light uncaging reaction enabled the light-inducible protein expression, the photo-manipulation of membrane potentials, and the subcellular-specific photo-release of small molecules.
AN IMPROVED PROCESS FOR THE PREPARATION OF BACLOFEN AND ITS INTERMEDIATE
-
Page/Page column 17, (2017/02/09)
The present invention provides an improved process for the preparation of 3-(4-chlorophenyl)-3- cyanopropanoic acid (compound (A)) and further its transformation to Baclofen (I). The process comprises reaction of compound (II) with Glyoxylic acid to obtain 3-(4-chlorophenyl)-3- cyanoacrylic acid (III); followed by the 'in- situ' reduction of (III) in the presence of a reducing agent to provide the compound (A). Alternatively, the compound (A) is obtained by the process comprising reacting 2-(4- chlorophenyl)acetonitrile (II) with haloacetic acid (IV) in the presence of a base. The compound 3-(4-chlorophenyl)-3-cyanopropanoic acid (A) undergoes hydrogenation in the presence of a metal catalyst and ammonia solution to provide Baclofen (I).
Catalytic Intermolecular Carboamination of Unactivated Alkenes via Directed Aminopalladation
Liu, Zhen,Wang, Yanyan,Wang, Zichen,Zeng, Tian,Liu, Peng,Engle, Keary M.
supporting information, p. 11261 - 11270 (2017/08/22)
An intermolecular 1,2-carboamination of unactivated alkenes proceeding via a Pd(II)/Pd(IV) catalytic cycle has been developed. To realize this transformation, a cleavable bidentate directing group is used to control the regioselectivity of aminopalladation and stabilize the resulting organopalladium(II) intermediate, such that oxidative addition to a carbon electrophile outcompetes potential β-hydride elimination. Under the optimized reaction conditions, a broad range of nitrogen nucleophiles and carbon electrophiles are compatible coupling partners in this reaction, affording moderate to high yields. The products of this reaction can be easily converted to free ?3-amino acids and ?3-lactams, both of which are common structural motifs found in drug molecules and bioactive compounds. Reaction kinetics and DFT calculations shed light on the mechanism of the reaction and explain empirically observed reactivity trends.
A balufen green industrial production method (by machine translation)
-
, (2017/05/02)
The invention discloses a balufen green preparation method, which belongs to the technical field of drug synthesis. The method to the chlorobenzene as a starting material, by Knoevenagel condensation, alkali hydrolysis, sub-amide, alkali hydrolysis and Hofmann degradation 5 step reaction make the consistent with the clinical pharmaceutical balufen. Raw materials of this invention extremely easy, low cost, simple synthesis operation, are basically all aqueous reaction under the condition of, environmental pollution is very small, high yield, is a brand new industrial production balufen method. (by machine translation)
Chemical assembly systems: Layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients
Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
supporting information, p. 678 - 682 (2015/03/04)
While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels - choice of starting material, reagent, or order of reaction modules - enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
β-Substituted γ-butyrolactams from mucochloric acid: Synthesis of (±)-baclofen and other γ-aminobutyric acids and useful building blocks
Biswas, Kallolmay,Gholap, Rajesh,Srinivas, Padakanti,Kanyal, Sachin,Sarma, Koushik Das
, p. 2538 - 2545 (2014/01/06)
In the course of our exploration of the application of mucohalic acids in organic synthesis, we reported the synthesis of α,β-dihalo-α, β-unsaturated γ-butyrolactams by reductive amination of a suitable mucohalic acid and a suitable amine. However, the functionalization of the α- and/or β-halogen was found to be elusive under Suzuki conditions that worked well with the corresponding γ-lactones. Although the corresponding β-aryl derivative was obtained under some of the modified Suzuki conditions tried, the yields were found to be very low. Next, the Suzuki coupling was performed on mucochloric acid prior to the reductive amination step. By careful control of the reaction conditions, only β-substitution was achieved to yield the corresponding β-aryl mucochloric acid. This could then be converted to the corresponding β-substituted γ-butyrolactam by reductive amination with 2,4-dimethoxybenzylamine (DMB-NH2) followed by reduction by nickel boride and subsequent deprotection of the DMB group. The resulting γ-butyrolactam could either be alkylated or hydrolyzed resulting in the corresponding β-substituted γ-aminobutyric acid. This methodology was extended to synthesize (±)-baclofen in five steps starting from mucochloric acid.
METHODS OF TREATING FRAGILE X SYNDROME, DOWN?S SYNDROME, AUTISM AND RELATED DISORDERS
-
, (2012/02/01)
Disclosed herein are methods of treating fragile X syndrome, fragile X-associated tremor/ataxia syndrome, Down?s syndrome and other forms of mental retardation, and/or autism comprising administering a GABA B agonist prodlug to a subject suffering therefrom. The GABAB agonist prodrugs can be compounds of Formula (I), (II) or (III) as disclosed herein
ALLOSTERIC PROTEIN KINASE MODULATORS
-
Page/Page column 94, (2010/04/30)
The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.
