2952-00-3

Basic information

• Product Name: (trans-4-AMinocyclohexyl)acetic acid
• Synonyms: (trans-4-AMinocyclohexyl)acetic acid;(trans-4-AMinocyclohexyl)acetic acid-3;trans-2-(4-Aminocyclohexyl);trans-4-Aminocyclohexaneacetic acid
• CAS NO: 2952-00-3
• Molecular Formula: C₈H₁₅NO₂
• Molecular Weight: 157.2102
• Mol File: 2952-00-3.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 301.3 °C at 760 mmHg
• Flash Point: 136 °C
• Appearance: /
• Density: 1.075 g/cm³
• Vapor Pressure: 0.000249mmHg at 25°C
• Refractive Index: 1.487
• CAS DataBase Reference: (trans-4-AMinocyclohexyl)acetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (trans-4-AMinocyclohexyl)acetic acid(2952-00-3)
• EPA Substance Registry System: (trans-4-AMinocyclohexyl)acetic acid(2952-00-3)

Safety Data

• Hazardous Substances Data: 2952-00-3(Hazardous Substances Data)

Usage

General Description

(Trans-4-Aminocyclohexyl)acetic acid, more commonly known as Norvaline, is an amino acid with the formula C8H15NO2. It is a structural isomer of the essential amino acid valine and is found in many proteins. It is a white, crystalline substance with a mildly sweet taste. Its most significant use is in the field of biochemistry where it assists in protein synthesis. It also has a potential role in tissue regeneration and muscle growth. Interestingly, it may have neuroprotective qualities, possibly useful in treating neurodegenerative diseases. Despite these potential benefits, it should be handled with care, as prolonged exposure could lead to skin, eye, and respiratory irritation.

InChI:InChI=1/C8H15NO2/c9-7-3-1-6(2-4-7)5-8(10)11/h6-7H,1-5,9H2,(H,10,11)/t6-,7-

Synthetic route

(trans-4-benzamino-cyclohexyl)-acetic acid ethyl ester → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
With methanol; barium dihydroxide

trans-2-(4-acetamidocyclohexyl)acetic acid (2901-44-2) → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
With sulfuric acid
With sodium hydroxide In butan-1-ol at 25 - 120℃; for 16.25h;

ethyl 2‐[(1r,4r)‐4‐aminocyclohexyl]acetate (76308-28-6) → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
With water for 12h; Heating;	1.46 g

trans-(4-Amino-cyclohexyl)-acetic acid ethyl ester (343775-23-5) → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: chloroform; aq. NaOH solution 2: barium hydroxide; aqueous methanol View Scheme

4-acetamidophenylacetic acid (18699-02-0) → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2 / PtO2 / acetic acid 2: aq. H2SO4 View Scheme

4-nitrobenzeneacetic acid (104-03-0) → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
With sodium hydroxide; hydrogen; nickel In water at 125 - 130℃; under 86258.6 - 97509.8 Torr; for 168h;
With palladium 10% on activated carbon; hydrogen In water at 20℃; under 3102.97 Torr; for 72h;
With palladium 10% on activated carbon; hydrogen at 20℃; under 3102.97 Torr; for 72h;
With 5%-palladium/activated carbon; hydrogen In 2-methyl-propan-1-ol at 25 - 55℃; under 3750.38 Torr; for 6.25h; Autoclave;	2.5 g

C12H19NO3 → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 5%-palladium/activated carbon; hydrogen / methanol / 3 h / 25 - 30 °C / 1500.15 - 2250.23 Torr 2: sodium hydroxide / water / 5 h / 25 - 30 °C 3: sodium hydroxide / butan-1-ol / 16.25 h / 25 - 120 °C View Scheme

ethyl 2-(trans/cis)-(4-acetamidocyclohexyl)acetate → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 5 h / 25 - 30 °C 2: sodium hydroxide / butan-1-ol / 16.25 h / 25 - 120 °C View Scheme

N-(4-oxocyclohexyl)acetamide (27514-08-5) → trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium tert-butylate / methanol / 1 h / 0 - 5 °C 1.2: 1 h / 0 - 5 °C 2.1: 5%-palladium/activated carbon; hydrogen / methanol / 3 h / 25 - 30 °C / 1500.15 - 2250.23 Torr 3.1: sodium hydroxide / water / 5 h / 25 - 30 °C 4.1: sodium hydroxide / butan-1-ol / 16.25 h / 25 - 120 °C View Scheme

but-3-enoyl chloride (1470-91-3) + trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → (4-But-3-enoylamino-cyclohexyl)-acetic acid (189504-66-3)

Conditions	Yield
With sodium hydroxide In water 1.) 0 deg C to 5 deg C, 2.) room temp., 20 min;	72%

2-chloroethyl isothiocyanate (1943-83-5) + trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → {4-[3-(2-Chloro-ethyl)-ureido]-cyclohexyl}-acetic acid (61367-24-6)

Conditions	Yield
With sodium hydroxide

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → {4-[3-Chloro-4-(2-chloro-ethylsulfanyl)-butyrylamino]-cyclohexyl}-acetic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 72 percent / NaOH / H2O / 1.) 0 deg C to 5 deg C, 2.) room temp., 20 min 2: CCl4 / -30 - -20 °C 3: nitromethane / 24 h / 60 - 70 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → {4-[4-Chloro-3-(2-chloro-ethylsulfanyl)-butyrylamino]-cyclohexyl}-acetic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: 72 percent / NaOH / H2O / 1.) 0 deg C to 5 deg C, 2.) room temp., 20 min 2: CCl4 / -30 - -20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → C11H18ClN3O4 (52320-89-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH 2: NaNO2, HCO2H / formic acid View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → trans-4-aminocyclohexylacetic acid hydrochloride (76325-96-7)

Conditions	Yield
With hydrogenchloride In water pH=5;

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → trans 2-{1-[4-(N-(tert-butoxycarbonyl))amino]cyclohexyl}ethyl acetate (946598-34-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → trans-2-(1-(4-(N-tert-butoxycarbonyl)amino)cyclohexyl)acetaldehyde (215790-29-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C 3: diisobutylaluminium hydride / toluene / 0.5 h / -78 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → Cariprazine (839712-12-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C 6: dichloromethane / 18 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: dichloromethane / 14 h / 5 - 30 °C 2: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran / 4 h / 25 - 30 °C / Inert atmosphere 3: boron trifluoride diethyl etherate; sodium tetrahydroborate / tetrahydrofuran / 1.75 h / -20 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: dichloromethane / 14 h / 5 - 30 °C 2.1: 1,1'-carbonyldiimidazole / 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran / 2 h / 25 - 30 °C / Inert atmosphere 2.2: 4 h / 25 - 30 °C / Inert atmosphere 3.1: sodium bis(2-methoxyethoxy)aluminium dihydride / 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran / 2 h / 0 - 5 °C / Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / 20 h / 25 - 30 °C View Scheme
Multi-step reaction with 6 steps 1.1: sodium hydroxide / 1,4-dioxane / 0.17 h / 0 - 5 °C 1.2: 3.16 h / 0 - 30 °C 2.1: 4-methyl-morpholine / dichloromethane / 4 h / -20 - -15 °C 3.1: hydrogenchloride / ethyl acetate / 12 h / 25 - 30 °C 4.1: triethylamine / dichloromethane / 0.17 h / 25 - 30 °C 4.2: 12 h / 25 - 30 °C 5.1: sodium bis(2-methoxyethoxy)aluminium dihydride / 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran / 2 h / 0 - 5 °C / Inert atmosphere 6.1: sodium tris(acetoxy)borohydride / 20 h / 25 - 30 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → tert-butyl (trans-4-(2-(7-nitro-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)carbamate

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → trans-2-(2-(1-4-(N-tert-butyloxycarbonyl)amino)cyclohexyl)ethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline (215790-43-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C 3: diisobutylaluminium hydride / toluene / 0.5 h / -78 °C 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → tert-butyl (trans-4-(2-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)ethyl)cyclohexyl)carbamate

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → trans N-tert-butoxycarbonyl-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethyl}-cyclohexylamine

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C 3: diisobutylaluminium hydride / toluene / 0.5 h / -78 °C 4: sodium tris(acetoxy)borohydride; N-ethyl-N,N-diisopropylamine / 1,2-dichloro-ethane / 20 °C / Inert atmosphere View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexanamine dihydrochloride

Conditions	Yield
Multi-step reaction with 5 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C View Scheme
Multi-step reaction with 5 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C 3: diisobutylaluminium hydride / toluene / 0.5 h / -78 °C 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere 5: trifluoroacetic acid / 1,2-dichloro-ethane / 16 h / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → 2-(2-(trans-4-aminocyclohexyl)ethyl)-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile dihydrochloride

Conditions	Yield
Multi-step reaction with 5 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → N-(trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)acetamide

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C 6: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → N-(trans-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)acetamide

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C 6: N-ethyl-N,N-diisopropylamine / dichloromethane / 2 h / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → ethyl (trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)carbamate

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C 6: triethylamine / dichloromethane / 14 h / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → isopropyl (trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)carbamate

Conditions

Yield

Multi-step reaction with 6 steps 1.1: hydrogenchloride / water / 2 h / Reflux 2.1: triethylamine / dichloromethane / 20 °C 3.1: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5.1: trifluoroacetic acid / dichloromethane / 20 °C 6.1: 1,1'-carbonyldiimidazole / acetonitrile; dichloromethane / 16 h / 20 °C / Inert atmosphere 6.2: Inert atmosphere; Reflux View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → isobutyl (trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)carbamate

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C 6: triethylamine / dichloromethane / 1 h / 20 °C / Inert atmosphere View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → tert-butyl (trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)-ethyl)cyclohexyl)carbamate

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 2 h / 20 °C 3: diisobutylaluminium hydride / toluene / 0.5 h / -78 °C 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C / Inert atmosphere View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → phenyl (trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)carbamate

Conditions	Yield
Multi-step reaction with 6 steps 1: hydrogenchloride / water / 2 h / Reflux 2: triethylamine / dichloromethane / 20 °C 3: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5: trifluoroacetic acid / dichloromethane / 20 °C 6: N-ethyl-N,N-diisopropylamine / dichloromethane / 14 h / 20 °C View Scheme

trans-2-(4-aminocyclohexyl)acetic acid (2952-00-3) → 3-(trans-4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1,1-dimethylurea

Conditions

Yield

Multi-step reaction with 6 steps 1.1: hydrogenchloride / water / 2 h / Reflux 2.1: triethylamine / dichloromethane / 20 °C 3.1: diisobutylaluminium hydride / toluene / -78 °C / Inert atmosphere 4.1: sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C 5.1: trifluoroacetic acid / dichloromethane / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; 1,1'-carbonyldiimidazole / tetrahydrofuran / 0.5 h / 20 °C / Inert atmosphere 6.2: 16 h / 20 °C / Inert atmosphere View Scheme

Upstream product

• 27514-08-5 N-(4-oxocyclohexyl)acetamide 
• 104-03-0 4-nitrobenzeneacetic acid 
• 18699-02-0 4-acetamidophenylacetic acid 
• 76308-28-6 ethyl 2‐[(1r,4r)‐4‐aminocyclohexyl]acetate 
• 2901-44-2 trans-2-(4-acetamidocyclohexyl)acetic acid 
• 343775-23-5 trans-(4-Amino-cyclohexyl)-acetic acid ethyl ester 

Downstream Products

• 76325-96-7 trans-4-aminocyclohexylacetic acid hydrochloride 

Relevant articles and documents

NOVEL PROCESSES FOR THE PREPARATION OF TRANS-N-{4-[2-[4-(2,3-DICHLOROPHENYL)PIPERAZINE-1-YL]ETHYL] CYCLOHEXYL}-N',N'-DIMETHYLUREA HYDROCHLORIDE AND POLYMORPHS THEREOF

The present invention relates to novel processes for the preparation of trans- N-{4-[2- [4-(2,3-dichloro phenyl) piperazine-1-yl] ethyl] cyclohexyl} -N',N'-dimethylurea hydrochloride represented by the following structural formula-1a and polymorphs thereof. (I) The present invention also relates to novel intermediate compounds which are useful for the preparation of compound of formula-1a.

A structure-activity analysis of biased agonism at the dopamine D2 receptor

Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl (trans-4-(2-(3,4-dihydroisoquinolin- 2(1H)-yl)ethyl)cyclohexyl)carbamate (4). This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.

cis- AND trans-4-AMINOCYCLOHEXYLACETIC ACIDS AND THEIR DIETHYLENIMIDO(THIO)PHOSPHORYL DERIVATIVES

-