143323-49-3

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 37763-23-8 D-2-p-hydroxyphenylglycine methyl ester 
• 57591-61-4 methyl (R)-2-amino-2-(4-hydroxyphenyl)acetate hydrochloride 
• 34619-03-9 tert-butyldicarbonate 
• 67-56-1 methanol 
• 22818-40-2 D-4-hydroxyphenylglycine 
• 43189-12-4 (R)-methyl 2-amino-2-(4-hydroxyphenyl)acetate 
• 186581-53-3 diazomethane 
• 53249-34-6 N-t-butoxycarbonyl-p-hydroxyphenylglycine 
• 6324-01-2 p-hydroxyphenylglycine 
• 27460-85-1 N-(tert-butoxycarbonyl)-D-(4-hydroxyphenyl)glycine 
• 18107-18-1 diazomethyl-trimethyl-silane 

Downstream Products

• 691889-35-7 (R)-N-(t-butoxycarbonyl)-4-(t-butyldimethylsiloxy)phenylglycinol 
• 178744-40-6 (S)-2-[(R)-2-tert-Butoxycarbonylamino-2-(4-hydroxy-phenyl)-acetylamino]-3-(4-fluoro-3-nitro-phenyl)-propionic acid methyl ester 
• 193073-85-7 methyl (R)-2-((tert-butoxycarbonyl)amino)-2-(4-methoxyphenyl)acetate 
• 458550-63-5 tert-butoxycarbonylamino-(4-{4-[4-(tert-butoxycarbonylamino-ethoxycarbonyl-methyl)-phenoxymethyl]-benzyloxy}-phenyl)-acetic acid ethyl ester 
• 458550-64-6 (4-{3,5-bis-[4-(tert-butoxycarbonylamino-ethoxycarbonyl-methyl)-phenoxymethyl]-benzyloxy}-phenyl)-tert-butoxycarbonylamino-acetic acid ethyl ester 
• 458550-61-3 tert-butoxycarbonylamino-(4-{2-[4-(tert-butoxycarbonylamino-ethoxycarbonyl-methyl)-phenoxymethyl]-benzyloxy}-phenyl)-acetic acid ethyl ester 
• 458550-62-4 tert-butoxycarbonylamino-(4-{3-[4-(tert-butoxycarbonylamino-ethoxycarbonyl-methyl)-phenoxymethyl]-benzyloxy}-phenyl)-acetic acid ethyl ester 
• 586413-61-8 (R)-N-(t-butoxycarbonyl)-4-(t-butyldimethylsiloxy)phenylglycine methyl ester 
• 761459-43-2 2,5-bis-[4-(tert-butoxycarbonylamino-ethoxycarbonyl-methyl)-phenoxymethyl]-benzoic acid ethyl ester 
• 313490-19-6 methyl N-tert-butoxycarbonyl-4-{[(trifluoromethyl)sulfonyl]oxy}-D-phenylglycinate 
• 906552-95-2 [1-(4-{4'-[4-(1-tert-butoxycarbonylamino-2-hydroxy-ethyl)-phenoxy]-1,1'-dioxy-[2,2']bipyridinyl-4-yloxy}-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester 
• 761459-44-3 2,5-Bis-[4-((R)-amino-ethoxycarbonyl-methyl)-phenoxymethyl]-benzoic acid ethyl ester 

Relevant academic research and scientific papers

Preparation method of (-) - Cytoxazone and (+) -4 - epi-Cytoxazone

The preparation method of (-) - Cytoxazone and (+) -4 - epi-Cytoxazone takes D - p-hydroxyphenylglycine as a raw material, the intermediate 2 is obtained through methyl esterification reaction under catalysis of thionyl chloride, and then the amino is protected with Boc anhydride to obtain the intermediate 3. The compound 4 is obtained by using potassium carbonate as a base and reacting with methyl iodide under reflux conditions. The methyl ester was reduced with sodium borohydride/lithium chloride to give the primary alcohol compound 5. An intermediate IBX is then obtained with 6 primary alcohol, then reacted with acetone cyanohydrin SN2 to give intermediate 7, and the intermediate 8 is obtained by reacting with the methanol solution of hydrogen chloride to obtain two five-membered ring compound compounds 9 and 10, respectively, with sodium borohydride to obtain (-) - Cytoxazone and its isomers (+) -4 - epi-Cytoxtoxtoxtoxol, respectively.

Bcl-2 INHIBITORS

Disclosed herein is a compound of Formula (I) for inhibiting Bcl-2 and treating disease associated with undesirable bcl-2 activity (Bcl-2 related diseases), a method of using the compounds disclosed herein for treating dysregulated apoptotic diseases incl

Compound, pharmaceutically acceptable salt thereof and medical application thereof

The invention belongs to the field of medicines, and particularly relates to a compound shown as a formula I or medicinal salt thereof. The invention also relates to application of the compound or themedicinal salt thereof in selectively inhibiting LF activity, resisting anthrax toxin toxicity and preventing or treating anthracnose.

Design, Synthesis, and Structure-Activity Relationship Studies of (4-Alkoxyphenyl)glycinamides and Bioisosteric 1,3,4-Oxadiazoles as GPR88 Agonists

Increasing evidence implicates the orphan G protein-coupled receptor 88 (GPR88) in a number of striatal-associated disorders. In this study, we report the design and synthesis of a series of novel (4-alkoxyphenyl)glycinamides (e.g., 31) and the corresponding 1,3,4-oxadiazole bioisosteres derived from the 2-AMPP scaffold (1) as GPR88 agonists. The 5-amino-1,3,4-oxadiazole derivatives (84, 88-90) had significantly improved potency and lower lipophilicity compared to 2-AMPP. Compound 84 had an EC50 of 59 nM in the GPR88 overexpressing cell-based cAMP assay. In addition, 84 had an EC50 of 942 nM in the [35S]GTPγS binding assay using mouse striatal membranes but was inactive in membranes from GPR88 knockout mice, even at a concentration of 100 μM. In vivo pharmacokinetic testing of 90 in rats revealed that the 5-amino-1,3,4-oxadiazole analogues may have limited brain permeability. Taken together, these results provide the basis for further optimization to develop a suitable agonist to probe GPR88 functions in the brain.

TYROSINE ANALOGUES DERIVATIVES AS RHO- KINASE INHIBITORS

The invention relates to compounds of formula (I) inhibiting Rho Kinase that are tyrosine analogues derivatives, methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof. Particularly the compounds of the invention may be useful in the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).

APOPTOSIS-INDUCING AGENTS

Provided are certain Bcl-2 inhibitors, pharmaceutical compositions thereof, and methods of use thereof.

Design, synthesis and pharmacological evaluation of 4-hydroxyphenylglycine and 4-hydroxyphenylglycinol derivatives as GPR88 agonists

The orphan receptor GPR88 is an attractive therapeutic target because of its implications in a number of basal ganglia-associated disorders. To date, pharmacological characterization of GPR88 has been limited due to the lack of potent and selective agonists and antagonists appropriate for CNS investigations. We have previously reported that GPR88 couples to Gαiproteins and modulates cAMP levels upon treatment with a small molecule agonist 2-PCCA. Recently, another chemotype of GPR88 agonist, represented by 2-AMPP [(2S)-N-((1R)-2-amino-1-(4-(2-methylpentyloxy)-phenyl)ethyl)-2-phenylpropanamide], has also been discovered. In this report, a new series of 2-AMPP structurally related 4-hydroxyphenylglycine and 4-hydroxyphenylglycinol derivatives have been designed and evaluated for agonist activity at GPR88. The structure-activity relationship (SAR) studies suggest that the amine group in 2-AMPP can be replaced by hydroxyl, ester and amide groups, resulting in analogues with good to moderate potency, whereas the phenyl group on the amide cap is essential for activity and has limited size, shape and electronic tolerance.

GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

Disclosed are a gonadotropin releasing hormone receptor antagonist and a pharmaceutical composition including the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease.

Discovery of novel 2,5-dioxoimidazolidine-based P2X7 receptor antagonists as constrained analogues of KN62

Novel 2,5-dioxoimidazolidine-based conformationally constrained analogues of KN62 (1) were developed as P2X7 receptor (P2X7R) antagonists using a rigidification strategy of the tyrosine backbone of 1. SAR analysis of the 2,5-dioxoimidazolidine scaffold indicated that piperidine substitution at the N3 position and no substitution at N1 position were preferable. Further optimization of the substituents at the piperidine nitrogen and the spacer around the skeleton resulted in several superior antagonists to 1, including 1-adamantanecarbonyl analogue 21i (IC50 = 23 nM in ethidium uptake assay; IC50 = 14 nM in IL-1β ELISA assay) and (3-CF3-4-Cl)benzoyl analogue (-)-21w (54 nM in ethidium uptake assay; 9 nM in IL-1β ELISA assay), which was more potent than the corresponding (+) isomer. Compound 21w displayed potent inhibitory activity in an ex vivo model of LTP-induced pain signaling in the spinal cord and significant anti-inflammatory activity in in vivo models of carrageenan-induced paw edema and type II collagen-induced joint arthritis.

GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

The present invention provides gonadotropin releasing hormone receptor antagonists and the pharmaceutical composition comprising the same, which can be useful in preventing or treating a sex hormone-related disease such as endometriosis, amenorrhea, irregular menstruation, uterine myoma, uterine fibroids, polycystic ovarian disease, lupus erythematous, hypertrichosis, precocious puberty, short stature, acne, alopecia, gonadal steroid-dependent neoplasms, gonadotropin-producing pituitary adenoma, sleep apnea, irritable bowel syndrome, premenstrual syndrome, benign prostatic hyperplasia, contraception, and infertility, as well as Alzheimer disease