Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5954_Библиотеки_им_академика_М_И_Перельмана
.pdf
(29) 6-Benzoyl-3-hydrazino-5,6,7,8-tetrahydropyrido[4,3-c]pyridazine or (3-hydrazine
-yl-7,7-dihydropyrido[4,3-c]pyridazine-6(5H)-yl)phenylmethanone
(30) 2-[3-(4-Chlorophenyl)-1-phenyl-1H-pyrazole-4-yl]acetic acid
(31) N
1
-(6-Methoxy-2-methylpyrimidine-1-methyl)sulfanilamide
(32) N
1
-(5-Methyl-1,3,4-thiadiazole-2-yl)sulfanilamide
(33) Ethyl methyl 4-(2,3-dichloro phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate
(34) 7-Chloro-N-(5-diethylamino)pentan-2-yl)quinazoline-4-amine
(35) 10-Chloro-11b-(2-chlorophenyl)-7-methyl-3,5,7,11b-tetrahydro-2H-oxazolo[3,2-
d]-1,4-benzodiazepine-6-one
(36) 3-(Acetoxymethyl)-7-[2-(2-thienyl)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]
oct-2-ene-2-carboxylic acid
B. Formulate the following drugs:
(1)
(2)
(3)
(4)
(5)
(6)
(7)
182 9 Solutions to the exercises
https://t.me/medicina_free
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
9.1 Exercises to Chapter 2 183
https://t.me/medicina_free
(18) (20)
(19)
9.2 Exercises to Chapter 4
1. (a) Modulative structural modification due to a ring size variation
(b) Modulative variation due to reorganization and dissociation of the rings
(c) Modulative structural variation by isomerization
(d) Modulative structural variation by formation of a rigid analog
(e) Conjunctive replication by formation of a hybrid or a molecular combination
(f) Structural modulative variation by bioisosterism
(g) Disjunctive replication
(h) Disjunctive replication
(i) Modulative structural variation by formation of a cycle
(j) Conjunctive replication: molecular duplication
(k) Modulative structural variation by bioisosterism
(l) Conjunctive replication by association of two molecules (antihypertensive +
diuretic drug)
(m) Disjunctive replication (simplification of the structure)
(n) Modulative structural variation due to the formation of a cycle
(o) Modulative variation by a bioisosteric change (suprophen: a drug with anal-
gesic and an anti-inflammatory property)
2. (a) Vinylogous: procaine and its active vinylogue
(b) Isosteres: change of the carbonyl and sulfone groups (meperidine and its iso-
stere that is also a hypnoanalgesic drug)
(c) Isosteres: indomethacin and oxametacin (an isosteric anti-inflammatory agent)
(d) Homologs: procaine and its inactive counterpart
(e) Isosteres: catechol and benzimidazole
184 9 Solutions to the exercises
https://t.me/medicina_free
(f) Isosteres: 4-dimethylaminoantipyrine and 4-isopropylantipyrine, both analge-
sic and antipyretic agents
(g) Homologs
(h) Isosteres: hypoxanthine and 6-mercaptopurine
(i) Isosteres: methaphenilene and methapyrilene
(j) Vinylogues: pethidine (meperidine) and its vinylogue
(k) Vinylogues: phenylbutazone and styrylbutazone
3. (a) Modification of pharmacokinetics by blocking the metabolism by the intro-
duction of fluorine atoms into the aromatic rings: longer duration of action.
The compound on the left is CGP52411, an enzymatic inhibitor that acts on the
active site of the epidermal growth factor receptor, useful as an antitumor
agent. This compound undergoes oxidative metabolism at the para-position
of the aromatic ring. The introduction of F resulted in CGP53353. This same
procedure was successfully applied in the synthesis of gefitinib, which is a
drug used for certain breast, lung, and other cancers.
(b) Transformation of an agonist into antagonist (hypoxanthine, a metabolite,
and 6-mercaptopurine, an antitumor agent by antagonism)
(c) Development of therapeutic copies: enalapril and its therapeutic copy, quinapril
(d) Activity change (homology allowed by chance the interaction with another bi-
ological target): dietazine, an H
1
antihistaminic drug, and chlorpromazine, a
neuroleptic change
(e) Reduction of toxicity: the change of chlorine atoms of the compound UK47265
by F atoms led to the antifungal fluconazole, lacking toxicity
(f) Improvement of distribution so that it reaches the organs where it has to ex-
ercise its action: mechlorethamine and melphalan
(g) Change of the spectrum of action: transformation of an agonist into an antag-
onist, by introduction of bulky groups (acetylcholine and propantheline)
(h) Improvement of distribution: the compound does not cross the blood–brain
barrier with the quaternization of nitrogen and acts only at the peripheral
level (scopolamine and scopolamine butylbromide)
9.3 Exercises to Chapter 5
1. (a)
9.3 Exercises to Chapter 5 185
https://t.me/medicina_free
(b)
(c)
(d)
(e)
186 9 Solutions to the exercises
https://t.me/medicina_free
(f)
(g)
(h)
2. (a)
9.3 Exercises to Chapter 5 187
https://t.me/medicina_free
(b)
(c)
(d)
(e)
188 9 Solutions to the exercises
https://t.me/medicina_free
3.
4. (a)
Hydrophobic interactions cause it to act as an antagonist.
(b)
D + R Ð
K
1
K
2
DR½ !
K
3
Biological response
Agonist: big K
1
≥ K
2
, K
3
Antagonist: K
1
≥ K
2
, K
3
=0
9.3 Exercises to Chapter 5 189
https://t.me/medicina_free
Partial agonist: small K
1
≥ K
2
, K
3
Inactive compound: K
1
≤ K
2
5. (a)
(b)
(c)
190 9 Solutions to the exercises
https://t.me/medicina_free
(d)
(e)
9.3 Exercises to Chapter 5 191
https://t.me/medicina_free
Соседние файлы в папке Библиотека им академика М.И. Перельмана