S T R U C T U R E - / E F F E
C T- R E L A T I O N S H I P
of some selected biologically active quinunclidine compounds |
Structure |
Name |
Application |
Reference |
 |
3-Quinuclidinone
methyliodide;
N-methyl-3-
oxoquinuclidinium
iodide
L9039 Quireston |
potent
inhibitor of
high-affinity choline
uptake (HAchU) in
synaptosomes; acetyl-
choline synthesis
inhibitor; weak pene-
tration of biological
membranes. |
Latoxan |
 |
N-methyl-3-hydroxy-
quinuclidinium
iodide
L 9036 Quirestol |
potent inhibitor of
high-affinity choline
uptake (HAChU) in
synaptosomes, bicyclic
inhibitor of Choline;
acetylcholine synthesis
inhibitor; weak pene-
tration of biological
membranes
|
Latoxan |
 |
3-Quinuclidinyl
acetat hydrochloride
Aceclidine
hydrochloride |
eyedrops,hypo-
tensive, cholinergic |
Laboratori
Mag S.p.A. |
 a |
3-Quinucliny
benzoat
hydrochlorideBenzoclidin
hydrochloride,
Oxylidin (um)
Oksilidin, Oxilidin |
antihypertensive,
sedative |
Negwer-No.
4029-00 |
 |
3-Quinuclidinyl
benzilat
code-name
US-Army: BZ |
incapacitating agent in
chemical warfare, des-
orientation, hallu-
cination, confused
state,high-affinity
muscarinic antagonist |
see also
J. Med. Chem. 1995, 38,
1711 |
|
 |
N-methyl-3-
[(Cyclohexylhydroxy
-phenylacetyl)oxy]
quinuclidinium
bromide
Droclinium bromide,
LM 204 |
anticholinergic, anti-
ulcer agent |
Negwer No:
8884-00
CFM-Co.
Farmaceutica
Milanese S.p.A.
Laboratori
Mag S.p.A.
Sifavitor S.p.A. |
 |
N-methyl-3-
quinuclidinyl benzilat bromide
Clidinium bromide,
Quarzan (bromide):
Ro 2-3773 |
anticholinergic,
spasmolytic |
Negwer No:
9236-00 |
 |
alpha-Methyl-alpha-
phenylbenzene-
acetic acid
quinuclidin-
3-yl ester hydro-
chloride
Aprolidine |
anticholinergic |
Negwer No:
8940-00 |
Structure |
Name |
Application |
Reference |
 |
[R-(R*,R*)]alpha-
(Hydroxymethyl)-
alpha-phenyl-1H-
Imidazole-1-acetic
acid quinuclidine-
3-yl ester
Sepatropate,
UK-88060 |
bronchodilator,
antichonlinergic |
Negwer No:
7194-00 |
 |
|
M3 muscarinic
antagonist, useful as a
preventive or remedy
for urologic diseases,
respiratory diseases or
digestive diseases
|
Yamanouchi
Pharmaceutical Co.patent
WO96/20194 |
 |
|
cholesterol-lowering
agent, potent activity
of inhibiting squalene
synthase without any
side effects |
Yamanouchi
Pharmaceutical
Co.
patent
WO96/26938 |
 |
(R*,R*)-(±)-3-
[6,11-Dihydro-
2-methyl-benzo[b,e]
thiepin-11-yl)oxy]
quinuclidine
VUFB-17088 |
antihistaminic |
Negwer No: 8938-00 |
 |
(R*,R*)-(±)-3-
[2-Chloro-6,11-
dihydrobenzo
[b,e]thiepin-
11-yl)oxy]
quinuclidine
VUFB - 17089 |
antidepressant |
Negwer No:
8273-00 |
 |
Spiro (quinuclidine-
3,5`-oxazolidin)-2`-
on |
for treatment of
schizophrenia
depressions,
sleeplessness,
anxiety, Alzheimer
disease, intellectual
impairment, neurotic
depressions |
Astra AB
patent
PCT-WO
96 06 098 |
 |
cis-2-Methylspiro
(1,3-oxathiolane-
5,3`)quinuclidine
AF 102 B |
muscarinic agonist,
phase III of clinical
trials (Alzheimer´s)
see
also Spiro-
oxathiolane quinuclidines for treatment of xerostomia
EP 689863 A1 960103
see
also Spiro-
oxathiolane
quinuclidines for
treatment of Sjoegren`s
syndrome
EP 578511 A1 940112 |
Heterocycles
1994, 38, 1889
Ishihara Sangyo
Kaisha, Ltd.
patent
EP 683168 A1
950519 |
 |
2`-Methylspiro
[quinuclidine -3,4`
-[1,3] dioxalane |
muscarinic agonist |
Kabi
Pharmacia
AB
Uppsala
Sweden
J. Med. Chem.
1992, 35,
1541 |
|
Structure |
Name |
Application |
Reference |
 |
3-(2-Furanyl)
quinclidin-2-ene |
antimuscarinic |
Pharmacia
& Upjohn AB
Uppsala Sweden
J. Med. Chem.
1997, 40,
3804 - also
J. Med. Chem.
1995, 38, 473 |
|
 |
3-(2,3-Dihydro-
benzofuran-
2-yl) quinuclidine |
antimuscarinic |
Pharmacia
& Upjohn AB
Uppsala Sweden
Chirality 1998 |
|
 |
3-(4-(6-methyl-
pyridazin-3-yl)
phenyl)
quinuclidine-3-ol |
squalen synthase inhibitor, inhibitor of
cholestorol bio-
synthesis, hyper-
cholerstorolämie,
return to normality of
high blood fat value |
Zeneca
Ltd GB
patent
PCT-WO
9 324 486
Zeneca see
also
Biochemical
Pharmacology
1996, 51, 14777 |
|
 |
3-Hydroxy-3-
(4-chinolin-
6-yl) phenyl
quinuclidine |
squalen synthase
inhibitor, artherio-
sclerosis, decreasing of
serum cholestorol |
Rhône-Poulenc
Rorer Pharma-
ceuticals Inc.
USA
patent
PCT-WO
95 31458 |
 |
|
squalen synthase inhibitor, inhibition of
cholestorol biosynthesis, treatment of artheriosclerosis, hyper-
cholestorlämie, ischämie |
Zeneca
Ltd GB
patent
PCT-WO
95 35295
see also
J. Med. Chem.
1996, 39, 2971 |
|
 |
3-[2-(2-allyl-4-
(2-ethoxycarbony-
lethyl)
phenyl)ethynyl]
quinuclidin-3-ol |
squalen synthase
inhibitor, inhibition of
cholestorol
bio-
synthesis
|
Zeneca
Pharmaceuticals
GBBioorganic &
Medicinal
Chemistry Letters
1997, 7, 597 |
|
 |
1,2,4-Triazine
quinuclidine |
high affinity
muscarinic
partial
agonist |
SmithKline
Beecham
PharmaceuticalsBioorganic
& Medicinal
Chemistry Letters
1994, 4, 1411 |
|
 |
3-(3-Methyl-1,2,4-
triazol-1-yl)
quinuclidine |
muscarinic
agonist /
antagonist,
also 1,2,3
triazols and tetrazols |
SmithKline
Beecham
PharmaceuticalsJ..Med.
Chem.
1992, 35,
128 |
|
Structure |
Name |
Application |
Reference |
 |
methylated
1,2,4- oxadiazole
quinuclidine /
methylated 1,2,4-
thiadiazole
quinuclidine |
muscarinic
agonist /
antagonist |
Merck Sharp
Dohme
GBJ. Chem. Soc.
Chem. Commun.
1991, 760 |
 |
|
potential
application
for treatment of
irritable bowel
syndrome |
Lilly Research
USAJ.
Med. Chem.
|
| 1997, 40, 538 |
.
Eur. J. Med. Chem. |
| 1996, 31, 221 |
|
 |
3-Quinuclidinyl
diphenyl carbinolFencarol
Quifenadine |
antihistaminic
and
antiallergic
agent,glutamate
solutions
for injections |
Olaine Chemical-
Pharmaceutical
Plant2114 Olaine
Latvia
patent:
RU 2045268 C1 951010 tsentr po
Khimii
Lekarstvennykh
Sredstv, Russia
see also
Izobreteniya
1995, 28, 127 |
 |
10(3-Quinuclidinyl methyl)-phenothiazine) Mequitazine |
antihistaminic,
sedative,anti-
depressant,
allergic
diseases, hayfever,
conjuctiva
catarrh,
nettle rash, Quincke-
oedema, itchsee also preparation
of phenotiazine
derivatives
patent:
JP 04169583 A2
920617
Yodogawa
Phamaceutical
Co., Ltd. Japan |
Negwer No:
7671-00Asahi Chemical Industry Co. Ltd., Japan
Sumika Fine Chemicals Co. Ltd. Japan
Rhône-Poulenc Rorer France, GB |
 |
[R-(Z)]-(+)-a-
(quinuclidin-3-yl)
-a-(methoximino)
acetonitril(SB 202026) |
selective muscarinic M1
agonist,
currently in
phase III
clinical trials
for the
treatment
of
senile
dementia of
the Alzheimer
type (SDAT) |
SmithKline
Beecham
PharmaceuticalsJ. Med.Chem.
1997, 40, 4265
J. Chem. Soc.
Chem. Commun.
1994, 2189 |
|
 |
3-(3-Hexyloxy-
pyrazin
-2-ylsulfanyl) quinuclidine |
centrally active
muscarinic agent |
American Home
Products Cor-
poration USApatent
US005512574A |
 |
3(R)-[2-
(6-trifluoromethyl
pyrazin)yl]
quinuclidine |
treatment of
neurological and
mental illnesses whose
clinical manifestations
are due to cholinergic
deficiency,
and for
lowering
intraocular
pressure. |
Merck Sharp
Dohme
GBpatent
US005384408A
see also:
Lilly research
J. Med. Chem.
1995, 38, 3469 |
 |
(3R)-3-
(6-chloropyrazin-
2-yl)quinuclidine |
selective
muscarinic
agonist |
Merck Sharp Dohme GB
J.Chem. Soc. Perkin
Trans |
| 1995, 1, 641 |
|
Structure |
Name |
Application |
Reference |
 |
|
substance P
anta-
gonist treatment
of gastrointestinal
disorders, central
nervous system
disorders,
asthma,
pain, migraine,
emesis,
urinary
incontinence |
Pfizer
Pharma-
ceuticals Inc.
USA
patent
WO 95/02595
|
 |
CP-96,345 |
selective nonpeptide
antagonist for the
human
neurokinin NK1
receptor,useful in
the treat-
ment of inflammatory
disorders, central
nervous system
disorders, asthma,
pain,
migraine.
treatment or
prevention of eye
disorder (glaucoma,
ocular hypertension,
miosis, excess of
lacrimation, hyperemia
and breakdown of the
blood
aqueous barrier) |
Merck Research
USAMerck Sharp
Dohme GB
Pfizer Pharma-
ceuticals Inc. USA
patent
WO 94/26740
patent
WO 96/14845
Bioorganic &
Medicinal Chemistry
Letters |
1995,
7, 1345 |
.
J. Med. Chem. |
| 1995, 38, 934 |
see also Merck
Research USA
|
European
Journal of
Pharmacology |
| 1997, 325,
253 |
.
Bioorganic &
Medicinal
Chemistry
Letters |
1993,
3, 1361 |
|
|
 |
Palonosetron |
5-HT3 receptor
antagonistanti-emetic
in
cancer chemotherapy |
Syntex USA 1996 |
 |
N-(quinuclidin-
3-yl)-4-amino-
3-chloro-
1,8-naphthalimid |
high affinity
5-HT3 receptor
antagonist,
5-HT4 receptor
agonist |
| Syntex USA
Bioorganic
& Medicinal
Chemistry Letters
1993,
3, 1375 |
|
 |
N-(quinuclidin-
3-yl)-2-(1-methyl-
1H-indol-3-yl)
-2-oxo-
acetamide |
high affinity
5-HT3 receptor
partial
agonist,
with a pKi
at 5-HT3
receptors in
rat brain
of 9.6 ± 0.2,
and greater than
1000-fold
selectivity
over a wide range of
other neurotransmitter receptors |
Syntex USA Roche
Bioscience
Bioorganic & Medicinal Chemistry Letters
1995, 5, 1853 |
 |
(R)-3-(6-Chloro-
1-isopropyl-
benzimidazole-
4-carboxamido)
quinuclidine |
high affinity
ligand for the (R)-zacopride binding site
(pKi 9.84 ± 0.42) |
Roche Bioscience
USABioorganic &
Medicinal
Chemistry
Letters |
| 1996, 6, 477 |
|
 |
Z-2-[3`chlorophenyl)
methylene]-3-
quinuclidinone hydrochlorideL9038 Penetran Cl |
inhibitor of
high-affinity
choline uptake (HAChU) in synaptosomes; acetylcholine synthesis
inhibitor;
good penetration
of biological membranes. |
Latoxan
France |
 |
1,6-Hexamethylene-
bis-(3-benzyl-
quinuclidinium) chloride
tetrahydrateL 9041 Diquine |
nicotinic cholinoreceptor antagonist at the neuromuscular junction;
curare-like ganglioblocker. Curare-form
competitive
anti-
depolarizing muscle
relaxant used for
muscle relaxation and
controlled
breathing
under narcosis during
surgical
operations.
Can be used for
tracheal
intubation. |
Latoxan France |
Structure |
Name |
Application |
Reference |
 |
[2-(4-Amino-5-
chloro-2-metho-
xybenzoxy)
ethyl-
quinuclidinium
bromide |
high affinity 5-HT4-receptor
agonist |
Sanofi Midy
FranceJ. Med. Chem. 1997, 40, 608 |
 |
|
treatment of migraine,
headache,
diarrhoea,
Alzheimer
disease,
schizophrenia,
depressions, anxiety,
mania, gastrointestinal
disorders,
addiction to
alcohol and
drugs |
Synthélabo SA
France 1998patent
FR 2719842 |
 |
1-(3-(10,11-
Dihydro-5H-
dibenz[b,f]
azepin-5-yl-1-
propyl)-3-
quinuclidinium-
carboxylate |
use for the clinical
treatment of painful,
hyperalgesic and/or
inflammatory
conditions in
which C-
fibers play a patho-
physiological
role by
elicting neurogenic
pain
or inflammation,
use for treatment
of insulin resistance
in non-insulin-
dependent
diabetes
mellitus
(NIDDM). |
Novo Nordisk A/S
Denmark patent
WO 96/31498 |
 |
3-Ethoxycarbonyl quinuclidine hydrochloride L
9064 Ethoquine |
AChR agonist,
rigid bicyclic
analog
of Ach
and ARECOLINE.
Good penetration
of
biological membranes.
Weak muscarinic
agonist, weak
nicotinic
antagonist |
Latoxan France |
 |
Quinine |
antimalarial,
analgesic, antipyretic |
Buchler GmbH
Braunschweig
Germany |
|
Quinidine |
cardiac depressant (antiarrhythmic) |
Buchler GmbH
Braunschweig
Germany |
 |
2,2,6,6-tetramethyl
quinuclidine hydrobromide L 9044 Temechine |
neuronal nicotinic
AChR antagonist
without action on
skeleton muscle
innervation,
hypotensive,
selectively
blocks
autonomic
ganglia,
the
adrenal medulla,
carotid
glomerules,
good penetration
of biological
membranes. |
Latoxan France |
 |
1,2,2,6,6-penta-
methyl
quinuclidinium
iodideL 9045 Quirestine (Imechine) |
nicotinic AChR
antagonist, potent
short-acting
ganglioblocker.
Short-acting
hypotensive used
in surgery for obtaining
hypotension of
the desired level and
duratio. In contrast to
Arphonad has
no
histamine-like activity
and direct vasodilatory
action. Less toxic than
Arphonad. In clinical
practise besides
surgery is used for
treatment of
pulmonary or cervical
edemas and cronical
hypertension caused
by acute renal
deficiency. Marked
absence
of tachicardia
and prolongation of
myorelaxant action of
other drugs. |
Latoxan France |
Structure |
Name |
Application |
Reference |
